1. health and fitness
2. disorders

HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use
LYRICA safely and effectively. See full prescribing information for
LYRICA.
LYRICA (pregabalin) Capsules, CV
LYRICA (pregabalin) Oral Solution, CV
Initial U.S. Approval: 2004

----------------------DOSAGE FORMS AND STRENGTHS----------------Capsules: 25mg, 50 mg, 75 mg, 100 mg, 150 mg, 200 mg, 225 mg, and
300 mg. (3)
Oral Solution: 20 mg/ mL. (3)

-------------------------CONTRAINDICATIONS---------------------------Known hypersensitivity to pregabalin or any of its components. (4)

----------------------WARNINGS AND PRECAUTIONS--------------------------------------------------INDICATIONS AND USAGE-------------------------





LYRICA is indicated for:
Neuropathic pain associated with diabetic peripheral neuropathy (DPN)
(1)
Postherpetic neuralgia (PHN) (1)
Adjunctive therapy for adult patients with partial onset seizures (1)
Fibromyalgia (1)
Neuropathic pain associated with spinal cord injury (1)
----------------------------DOSAGE AND ADMINISTRATION------------------


For all indications, begin dosing at 150 mg/day. (2.1, 2.2, 2.3, 2.4, 2.5)
Dosing recommendations:
INDICATION
Dosing
Maximum Dose
Regimen
3 divided doses
300 mg/day within 1
DPN Pain (2.1)
per day
week
300 mg/day within 1
2 or 3 divided
week. Maximum dose of
PHN (2.2)
doses per day
600 mg/day.
Adjunctive Therapy for
Adult Patients with Partial
2 or 3 divided
Maximum dose of 600
Onset Seizures (2.3)
doses per day
mg/day.
300 mg/day within 1
week.
2 divided doses
Maximum dose of 450
Fibromyalgia (2.4)
per day
mg/day.
300 mg/day within 1
Neuropathic Pain Associated 2 divided doses
week. Maximum dose of
with Spinal Cord Injury (2.5) per day
600 mg/day.


Dose should be adjusted in patients with reduced renal function. (2.6)
Oral Solution Concentration and Dispensing (2.7)






Angioedema (e.g. swelling of the throat, head and neck) can occur, and
may be associated with life-threatening respiratory compromise requiring
emergency treatment. Discontinue LYRICA immediately in these cases.
(5.1)
Hypersensitivity reactions (e.g. hives, dyspnea, and wheezing) can
occur. Discontinue LYRICA immediately in these patients. (5.2)
Increased seizure frequency may occur in patients with seizure disorders
if LYRICA is rapidly discontinued. Withdraw LYRICA gradually over a
minimum of 1 week. (5.3)
Antiepileptic drugs, including LYRICA, increase the risk of suicidal
thoughts or behavior. (5.4)
LYRICA may cause peripheral edema. Exercise caution when coadministering LYRICA and thiazolidinedione antidiabetic agents. (5.5)
LYRICA may cause dizziness and somnolence and impair patients’
ability to drive or operate machinery.(5.6)
----------------------------ADVERSE REACTIONS----------------------Most common adverse reactions (≥ 5% and twice placebo) are dizziness,
somnolence, dry mouth, edema, blurred vision, weight gain and thinking
abnormal (primarily difficulty with concentration/attention). (6.1)
To report SUSPECTED ADVERSE REACTIONS, contact Pfizer at
(800) 438-1985 or FDA at 1-800-FDA-1088 or
www.fda.gov/medwatch

-----------------------USE IN SPECIFIC POPULATIONS----------------To enroll in the North American Antiepileptic Drug Pregnancy Registry
call 1-888-233-2334 (toll free). (8.1 )
See 17 for PATIENT COUNSELING INFORMATION and FDAapproved Medication Guide
Revised: 12/2013
FULL PRESCRIBING INFORMATION: CONTENTS*
1 INDICATIONS AND USAGE
2 DOSAGE AND ADMINISTRATION
2.1 Neuropathic Pain Associated with Diabetic Peripheral
Neuropathy
2.2 Postherpetic Neuralgia
2.3 Adjunctive Therapy for Adult Patients with Partial Onset
Seizures
2.4 Fibromyalgia
2.5 Neuropathic Pain Associated with Spinal Cord Injury
2.6 Patients with Renal Impairment
2.7Oral Solution Concentration and Dispensing
3 DOSAGE FORMS AND STRENGTHS
4 CONTRAINDICATIONS
5 WARNINGS AND PRECAUTIONS
5.1 Angioedema
5.2 Hypersensitivity
5.3 Withdrawal of Antiepileptic Drugs (AEDs)
5.4 Suicidal Behavior and Ideation
5.5 Peripheral Edema
5.6 Dizziness and Somnolence
5.7 Weight Gain
5.8 Abrupt or Rapid Discontinuation
5.9 Tumorigenic Potential
5.10 Ophthalmological Effects
5.11 Creatine Kinase Elevations
5.12 Decreased Platelet Count
5.13 PR Interval Prolongation
6 ADVERSE REACTIONS
6.1 Clinical Trial Experience
6.2 Postmarketing Experience
7 DRUG INTERACTIONS
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
8.2 Labor and Delivery
8.3 Nursing Mothers
8.4 Pediatric Use
8.5 Geriatric Use
* Sections or subsections omitted from the full prescribing information are not list
9 DRUG ABUSE AND DEPENDENCE
9.1 Controlled Substance
9.2 Abuse
9.3 Dependence
10 OVERDOSAGE
11 DESCRIPTION
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
12.3 Pharmacokinetics
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
13.2 Animal Toxicology and/or Pharmacology
14 CLINICAL STUDIES
14.1 Neuropathic Pain Associated with Diabetic Peripheral
Neuropathy
14.2 Postherpetic Neuralgia
14.3 Adjunctive Therapy for Adult Patients with Partial
Onset Seizures
14.4 Management of Fibromyalgia
14.5 Neuropathic Pain Associated with Spinal Cord Injury
16 HOW SUPPLIED/STORAGE AND HANDLING
17 PATIENT COUNSELING INFORMATION
17.1 Medication Guide
17.2 Angioedema
17.3 Hypersensitivity
17.4 Suicidal Thinking and Behavior
17.5 Dizziness and Somnolence
17.6 Weight Gain and Edema
17.7 Abrupt or Rapid Discontinuation
17.8 Ophthalmological Effects
17.9 Creatine Kinase Elevations
17.10 CNS Depressants
17.11 Alcohol
17.12 Use in Pregnancy
17.13 Male Fertility
17.14 Dermatopathy
FULL PRESCRIBING INFORMATION
1 INDICATIONS AND USAGE
LYRICA is indicated for:

Management of neuropathic pain associated with diabetic peripheral
neuropathy

Management of postherpetic neuralgia

Adjunctive therapy for adult patients with partial onset seizures

Management of fibromyalgia

Management of neuropathic pain associated with spinal cord injury
2 DOSAGE AND ADMINISTRATION
LYRICA is given orally with or without food.
When discontinuing LYRICA, taper gradually over a minimum of 1 week.
2.1 Neuropathic Pain Associated with Diabetic Peripheral Neuropathy
The maximum recommended dose of LYRICA is 100 mg three times a day (300 mg/day) in
patients with creatinine clearance of at least 60 mL/min. Begin dosing at 50 mg three times a day
(150 mg/day). The dose may be increased to 300 mg/day within 1 week based on efficacy and
tolerability. Because LYRICA is eliminated primarily by renal excretion, adjust the dose in
patients with reduced renal function [see Dosage and Administration (2.6)].
Although LYRICA was also studied at 600 mg/day, there is no evidence that this dose confers
additional significant benefit and this dose was less well tolerated. In view of the dose-dependent
adverse reactions, treatment with doses above 300 mg/day is not recommended [see Adverse
Reactions (6.1)].
2.2 Postherpetic Neuralgia
The recommended dose of LYRICA is 75 to 150 mg two times a day, or 50 to 100 mg three
times a day (150 to 300 mg/day) in patients with creatinine clearance of at least 60 mL/min.
Begin dosing at 75 mg two times a day, or 50 mg three times a day (150 mg/day). The dose may
be increased to 300 mg/day within 1 week based on efficacy and tolerability. Because LYRICA
is eliminated primarily by renal excretion, adjust the dose in patients with reduced renal function
[see Dosage and Administration (2.6)].
Patients who do not experience sufficient pain relief following 2 to 4 weeks of treatment with
300 mg/day, and who are able to tolerate LYRICA, may be treated with up to 300 mg two times
a day, or 200 mg three times a day (600 mg/day). In view of the dose-dependent adverse
reactions and the higher rate of treatment discontinuation due to adverse reactions, reserve
dosing above 300 mg/day for those patients who have on-going pain and are tolerating 300 mg
daily [see Adverse Reactions (6.1)].
2.3 Adjunctive Therapy for Adult Patients with Partial Onset Seizures
LYRICA at doses of 150 to 600 mg/day has been shown to be effective as adjunctive therapy in
the treatment of partial onset seizures in adults. Both the efficacy and adverse event profiles of
LYRICA have been shown to be dose-related. Administer the total daily dose in two or three
divided doses. In general, it is recommended that patients be started on a total daily dose no
greater than 150 mg/day (75 mg two times a day, or 50 mg three times a day). Based on
individual patient response and tolerability, the dose may be increased to a maximum dose of
600 mg/day.
Because LYRICA is eliminated primarily by renal excretion, adjust the dose in patients with
reduced renal function [see Dosage and Administration (2.6)].
The effect of dose escalation rate on the tolerability of LYRICA has not been formally studied.
The efficacy of add-on LYRICA in patients taking gabapentin has not been evaluated in
controlled trials. Consequently, dosing recommendations for the use of LYRICA with
gabapentin cannot be offered.
2.4 Management of Fibromyalgia
The recommended dose of LYRICA for fibromyalgia is 300 to 450 mg/day. Begin dosing at 75
mg two times a day (150 mg/day). The dose may be increased to 150 mg two times a day (300
mg/day) within 1 week based on efficacy and tolerability. Patients who do not experience
sufficient benefit with 300 mg/day may be further increased to 225 mg two times a day (450
mg/day). Although LYRICA was also studied at 600 mg/day, there is no evidence that this dose
confers additional benefit and this dose was less well tolerated. In view of the dose-dependent
adverse reactions, treatment with doses above 450 mg/day is not recommended [see Adverse
Reactions (6.1)]. Because LYRICA is eliminated primarily by renal excretion, adjust the dose in
patients with reduced renal function [see Dosage and Administration (2.6)].
2.5 Neuropathic Pain Associated with Spinal Cord Injury
The recommended dose range of LYRICA for the treatment of neuropathic pain associated with
spinal cord injury is 150 to 600 mg/day. The recommended starting dose is 75 mg two times a
day (150 mg/day). The dose may be increased to 150 mg two times a day (300 mg/day) within 1
week based on efficacy and tolerability. Patients who do not experience sufficient pain relief
after 2 to 3 weeks of treatment with 150 mg two times a day and who tolerate LYRICA may be
treated with up to 300 mg two times a day [see Clinical Studies (14.5)]. Because LYRICA is
eliminated primarily by renal excretion, adjust the dose in patients with reduced renal function
[see Dosage and Administration (2.6)].
2.6 Patients with Renal Impairment
In view of dose-dependent adverse reactions and since LYRICA is eliminated primarily by renal
excretion, adjust the dose in patients with reduced renal function. Base the dose adjustment in
patients with renal impairment on creatinine clearance (CLcr), as indicated in Table 1. To use
this dosing table, an estimate of the patient's CLcr in mL/min is needed. CLcr in mL/min may be
estimated from serum creatinine (mg/dL) determination using the Cockcroft and Gault equation:
Next, refer to the Dosage and Administration section to determine the recommended total daily
dose based on indication, for a patient with normal renal function (CLcr ≥60 mL/min). Then
refer to Table 1 to determine the corresponding renal adjusted dose.
(For example: A patient initiating LYRICA therapy for postherpetic neuralgia with normal renal
function (CLcr ≥60 mL/min), receives a total daily dose of 150 mg/day pregabalin. Therefore, a
renal impaired patient with a CLcr of 50 mL/min would receive a total daily dose of 75 mg/day
pregabalin administered in two or three divided doses.)
For patients undergoing hemodialysis, adjust the pregabalin daily dose based on renal function.
In addition to the daily dose adjustment, administer a supplemental dose immediately following
every 4-hour hemodialysis treatment (see Table 1).
Table 1. Pregabalin Dosage Adjustment Based on Renal Function
Creatinine Clearance (CLcr)
Total Pregabalin Daily Dose
Dose Regimen
(mL/min)
(mg/day)*
≥60
150
300
450
600
BID or TID
30–60
75
150
225
300
BID or TID
15–30
25–50
75
100–150
150
QD or BID
<15
25
25–50
50–75
75
QD
Supplementary dosage following hemodialysis (mg)†
Patients on the 25 mg QD regimen: take one supplemental dose of 25 mg or 50 mg
Patients on the 25–50 mg QD regimen: take one supplemental dose of 50 mg or 75 mg
Patients on the 50–75 mg QD regimen: take one supplemental dose of 75 mg or 100 mg
Patients on the 75 mg QD regimen: take one supplemental dose of 100 mg or 150 mg
TID= Three divided doses; BID = Two divided doses; QD = Single daily dose.
* Total daily dose (mg/day) should be divided as indicated by dose regimen to provide mg/dose.
†
Supplementary dose is a single additional dose.
2.7 Oral Solution Concentration and Dispensing
The oral solution is 20 mg pregabalin per milliliter (mL) and prescriptions should be written in
milligrams (mg). The pharmacist will calculate the applicable dose in mL for dispensing (e.g.,
150 mg equals 7.5 mL oral solution).
3 DOSAGE FORMS AND STRENGTHS
Capsules: 25 mg, 50 mg, 75 mg, 100 mg, 150 mg, 200 mg, 225 mg, and 300 mg
Oral Solution: 20 mg/mL
[see Description (11) and How Supplied/Storage and Handling (16)].
4 CONTRAINDICATIONS
LYRICA is contraindicated in patients with known hypersensitivity to pregabalin or any of its
components. Angioedema and hypersensitivity reactions have occurred in patients receiving
pregabalin therapy.
5 WARNINGS AND PRECAUTIONS
5.1 Angioedema
There have been postmarketing reports of angioedema in patients during initial and chronic
treatment with LYRICA. Specific symptoms included swelling of the face, mouth (tongue, lips,
and gums), and neck (throat and larynx). There were reports of life-threatening angioedema with
respiratory compromise requiring emergency treatment. Discontinue LYRICA immediately in
patients with these symptoms.
Exercise caution when prescribing LYRICA to patients who have had a previous episode of
angioedema. In addition, patients who are taking other drugs associated with angioedema (e.g.,
angiotensin converting enzyme inhibitors [ACE-inhibitors]) may be at increased risk of
developing angioedema.
5.2 Hypersensitivity
There have been postmarketing reports of hypersensitivity in patients shortly after initiation of
treatment with LYRICA. Adverse reactions included skin redness, blisters, hives, rash, dyspnea,
and wheezing. Discontinue LYRICA immediately in patients with these symptoms.
5.3 Withdrawal of Antiepileptic Drugs (AEDs)
As with all AEDs, withdraw LYRICA gradually to minimize the potential of increased seizure
frequency in patients with seizure disorders. If LYRICA is discontinued, taper the drug gradually
over a minimum of 1 week.
5.4 Suicidal Behavior and Ideation
Antiepileptic drugs (AEDs), including LYRICA, increase the risk of suicidal thoughts or
behavior in patients taking these drugs for any indication. Monitor patients treated with any AED
for any indication for the emergence or worsening of depression, suicidal thoughts or behavior,
and/or any unusual changes in mood or behavior.
Pooled analyses of 199 placebo-controlled clinical trials (mono- and adjunctive therapy) of 11
different AEDs showed that patients randomized to one of the AEDs had approximately twice
the risk (adjusted Relative Risk 1.8, 95% CI:1.2, 2.7) of suicidal thinking or behavior compared
to patients randomized to placebo. In these trials, which had a median treatment duration of 12
weeks, the estimated incidence rate of suicidal behavior or ideation among 27,863 AED-treated
patients was 0.43%, compared to 0.24% among 16,029 placebo-treated patients, representing an
increase of approximately one case of suicidal thinking or behavior for every 530 patients
treated. There were four suicides in drug-treated patients in the trials and none in placebo-treated
patients, but the number is too small to allow any conclusion about drug effect on suicide.
The increased risk of suicidal thoughts or behavior with AEDs was observed as early as one
week after starting drug treatment with AEDs and persisted for the duration of treatment
assessed. Because most trials included in the analysis did not extend beyond 24 weeks, the risk
of suicidal thoughts or behavior beyond 24 weeks could not be assessed.
The risk of suicidal thoughts or behavior was generally consistent among drugs in the data
analyzed. The finding of increased risk with AEDs of varying mechanisms of action and across a
range of indications suggests that the risk applies to all AEDs used for any indication. The risk
did not vary substantially by age (5-100 years) in the clinical trials analyzed.
Table 2 shows absolute and relative risk by indication for all evaluated AEDs.
Table 2. Risk by indication for antiepileptic drugs in the pooled analysis
Indication
Placebo Patients Drug Patients
Relative Risk:
with Events Per with Events Per Incidence of Events in
1000 Patients
1000 Patients
Drug
Patients/Incidence in
Placebo Patients
Epilepsy
1.0
3.4
3.5
Risk Difference:
Additional Drug
Patients with
Events Per 1000
Patients
2.4
Psychiatric
5.7
8.5
1.5
2.9
Other
1.0
1.8
1.9
0.9
Total
2.4
4.3
1.8
1.9
The relative risk for suicidal thoughts or behavior was higher in clinical trials for epilepsy than in
clinical trials for psychiatric or other conditions, but the absolute risk differences were similar for
the epilepsy and psychiatric indications.
Anyone considering prescribing LYRICA or any other AED must balance the risk of suicidal
thoughts or behavior with the risk of untreated illness. Epilepsy and many other illnesses for
which AEDs are prescribed are themselves associated with morbidity and mortality and an
increased risk of suicidal thoughts and behavior. Should suicidal thoughts and behavior emerge
during treatment, the prescriber needs to consider whether the emergence of these symptoms in
any given patient may be related to the illness being treated.
Inform patients, their caregivers, and families that LYRICA and other AEDs increase the risk of
suicidal thoughts and behavior and advise them of the need to be alert for the emergence or
worsening of the signs and symptoms of depression, any unusual changes in mood or behavior,
or the emergence of suicidal thoughts, behavior, or thoughts about self-harm. Report behaviors
of concern immediately to healthcare providers.
5.5 Peripheral Edema
LYRICA treatment may cause peripheral edema. In short-term trials of patients without
clinically significant heart or peripheral vascular disease, there was no apparent association
between peripheral edema and cardiovascular complications such as hypertension or congestive
heart failure. Peripheral edema was not associated with laboratory changes suggestive of
deterioration in renal or hepatic function.
In controlled clinical trials the incidence of peripheral edema was 6% in the LYRICA group
compared with 2% in the placebo group. In controlled clinical trials, 0.5% of LYRICA patients
and 0.2% placebo patients withdrew due to peripheral edema.
Higher frequencies of weight gain and peripheral edema were observed in patients taking both
LYRICA and a thiazolidinedione antidiabetic agent compared to patients taking either drug
alone. The majority of patients using thiazolidinedione antidiabetic agents in the overall safety
database were participants in studies of pain associated with diabetic peripheral neuropathy. In
this population, peripheral edema was reported in 3% (2/60) of patients who were using
thiazolidinedione antidiabetic agents only, 8% (69/859) of patients who were treated with
LYRICA only, and 19% (23/120) of patients who were on both LYRICA and thiazolidinedione
antidiabetic agents. Similarly, weight gain was reported in 0% (0/60) of patients on
thiazolidinediones only; 4% (35/859) of patients on LYRICA only; and 7.5% (9/120) of patients
on both drugs.
As the thiazolidinedione class of antidiabetic drugs can cause weight gain and/or fluid retention,
possibly exacerbating or leading to heart failure, exercise caution when co-administering
LYRICA and these agents.
Because there are limited data on congestive heart failure patients with New York Heart
Association (NYHA) Class III or IV cardiac status, exercise caution when using LYRICA in
these patients.
5.6 Dizziness and Somnolence
LYRICA may cause dizziness and somnolence. Inform patients that LYRICA-related dizziness
and somnolence may impair their ability to perform tasks such as driving or operating machinery
[see Patient Counseling Information (17.5)].
In the LYRICA controlled trials, dizziness was experienced by 30% of LYRICA-treated patients
compared to 8% of placebo-treated patients; somnolence was experienced by 23% of LYRICAtreated patients compared to 8% of placebo-treated patients. Dizziness and somnolence generally
began shortly after the initiation of LYRICA therapy and occurred more frequently at higher
doses. Dizziness and somnolence were the adverse reactions most frequently leading to
withdrawal (4% each) from controlled studies. In LYRICA-treated patients reporting these
adverse reactions in short-term, controlled studies, dizziness persisted until the last dose in 30%
and somnolence persisted until the last dose in 42% of patients [see Drug Interactions (7)].
5.7 Weight Gain
LYRICA treatment may cause weight gain. In LYRICA controlled clinical trials of up to 14
weeks, a gain of 7% or more over baseline weight was observed in 9% of LYRICA-treated
patients and 2% of placebo-treated patients. Few patients treated with LYRICA (0.3%) withdrew
from controlled trials due to weight gain. LYRICA associated weight gain was related to dose
and duration of exposure, but did not appear to be associated with baseline BMI, gender, or age.
Weight gain was not limited to patients with edema [see Warnings and Precautions (5.5)].
Although weight gain was not associated with clinically important changes in blood pressure in
short-term controlled studies, the long-term cardiovascular effects of LYRICA-associated weight
gain are unknown.
Among diabetic patients, LYRICA-treated patients gained an average of 1.6 kg (range: -16 to
16 kg), compared to an average 0.3 kg (range: -10 to 9 kg) weight gain in placebo patients. In a
cohort of 333 diabetic patients who received LYRICA for at least 2 years, the average weight
gain was 5.2 kg.
While the effects of LYRICA-associated weight gain on glycemic control have not been
systematically assessed, in controlled and longer-term open label clinical trials with diabetic
patients, LYRICA treatment did not appear to be associated with loss of glycemic control (as
measured by HbA1C).
5.8 Abrupt or Rapid Discontinuation
Following abrupt or rapid discontinuation of LYRICA, some patients reported symptoms
including insomnia, nausea, headache, anxiety, hyperhidrosis, and diarrhea. Taper LYRICA
gradually over a minimum of 1 week rather than discontinuing the drug abruptly.
5.9 Tumorigenic Potential
In standard preclinical in vivo lifetime carcinogenicity studies of LYRICA, an unexpectedly high
incidence of hemangiosarcoma was identified in two different strains of mice [see Nonclinical
Toxicology (13.1)]. The clinical significance of this finding is unknown. Clinical experience
during LYRICA’s premarketing development provides no direct means to assess its potential for
inducing tumors in humans.
In clinical studies across various patient populations, comprising 6396 patient-years of exposure
in patients >12 years of age, new or worsening-preexisting tumors were reported in 57 patients.
Without knowledge of the background incidence and recurrence in similar populations not
treated with LYRICA, it is impossible to know whether the incidence seen in these cohorts is or
is not affected by treatment.
5.10 Ophthalmological Effects
In controlled studies, a higher proportion of patients treated with LYRICA reported blurred
vision (7%) than did patients treated with placebo (2%), which resolved in a majority of cases
with continued dosing. Less than 1% of patients discontinued LYRICA treatment due to visionrelated events (primarily blurred vision).
Prospectively planned ophthalmologic testing, including visual acuity testing, formal visual field
testing and dilated funduscopic examination, was performed in over 3600 patients. In these
patients, visual acuity was reduced in 7% of patients treated with LYRICA, and 5% of placebotreated patients. Visual field changes were detected in 13% of LYRICA-treated, and 12% of
placebo-treated patients. Funduscopic changes were observed in 2% of LYRICA-treated and 2%
of placebo-treated patients.
Although the clinical significance of the ophthalmologic findings is unknown, inform patients to
notify their physician if changes in vision occur. If visual disturbance persists, consider further
assessment. Consider more frequent assessment for patients who are already routinely monitored
for ocular conditions [see Patient Counseling Information (17.8)].
5.11 Creatine Kinase Elevations
LYRICA treatment was associated with creatine kinase elevations. Mean changes in creatine
kinase from baseline to the maximum value were 60 U/L for LYRICA-treated patients and
28 U/L for the placebo patients. In all controlled trials across multiple patient populations, 1.5%
of patients on LYRICA and 0.7% of placebo patients had a value of creatine kinase at least three
times the upper limit of normal. Three LYRICA treated subjects had events reported as
rhabdomyolysis in premarketing clinical trials. The relationship between these myopathy events
and LYRICA is not completely understood because the cases had documented factors that may
have caused or contributed to these events. Instruct patients to promptly report unexplained
muscle pain, tenderness, or weakness, particularly if these muscle symptoms are accompanied by
malaise or fever. Discontinue treatment with LYRICA if myopathy is diagnosed or suspected or
if markedly elevated creatine kinase levels occur.
5.12 Decreased Platelet Count
LYRICA treatment was associated with a decrease in platelet count. LYRICA-treated subjects
experienced a mean maximal decrease in platelet count of 20 × 103/µL, compared to 11 × 103/µL
in placebo patients. In the overall database of controlled trials, 2% of placebo patients and 3% of
LYRICA patients experienced a potentially clinically significant decrease in platelets, defined as
20% below baseline value and <150 × 103/µL. A single LYRICA treated subject developed
severe thrombocytopenia with a platelet count less than 20 x 103/ µL. In randomized controlled
trials, LYRICA was not associated with an increase in bleeding-related adverse reactions.
5.13 PR Interval Prolongation
LYRICA treatment was associated with PR interval prolongation. In analyses of clinical trial
ECG data, the mean PR interval increase was 3–6 msec at LYRICA doses ≥300 mg/day. This
mean change difference was not associated with an increased risk of PR increase ≥25% from
baseline, an increased percentage of subjects with on-treatment PR >200 msec, or an increased
risk of adverse reactions of second or third degree AV block.
Subgroup analyses did not identify an increased risk of PR prolongation in patients with baseline
PR prolongation or in patients taking other PR prolonging medications. However, these analyses
cannot be considered definitive because of the limited number of patients in these categories.
6 ADVERSE REACTIONS
6.1 Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates
observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials
of another drug and may not reflect the rates observed in practice.
In all controlled and uncontrolled trials across various patient populations during the
premarketing development of LYRICA, more than 10,000 patients have received LYRICA.
Approximately 5000 patients were treated for 6 months or more, over 3100 patients were treated
for 1 year or longer, and over 1400 patients were treated for at least 2 years.
Adverse Reactions Most Commonly Leading to Discontinuation in All Premarketing Controlled
Clinical Studies
In premarketing controlled trials of all populations combined, 14% of patients treated with
LYRICA and 7% of patients treated with placebo discontinued prematurely due to adverse
reactions. In the LYRICA treatment group, the adverse reactions most frequently leading to
discontinuation were dizziness (4%) and somnolence (4%). In the placebo group, 1% of patients
withdrew due to dizziness and <1% withdrew due to somnolence. Other adverse reactions that
led to discontinuation from controlled trials more frequently in the LYRICA group compared to
the placebo group were ataxia, confusion, asthenia, thinking abnormal, blurred vision,
incoordination, and peripheral edema (1% each).
Most Common Adverse Reactions in All Premarketing Controlled Clinical Studies
In premarketing controlled trials of all patient populations combined, dizziness, somnolence, dry
mouth, edema, blurred vision, weight gain, and "thinking abnormal" (primarily difficulty with
concentration/attention) were more commonly reported by subjects treated with LYRICA than
by subjects treated with placebo (≥5% and twice the rate of that seen in placebo).
Controlled Studies with Neuropathic Pain Associated with Diabetic Peripheral Neuropathy
Adverse Reactions Leading to Discontinuation
In clinical trials in patients with neuropathic pain associated with diabetic peripheral neuropathy,
9% of patients treated with LYRICA and 4% of patients treated with placebo discontinued
prematurely due to adverse reactions. In the LYRICA treatment group, the most common
reasons for discontinuation due to adverse reactions were dizziness (3%) and somnolence (2%).
In comparison, <1% of placebo patients withdrew due to dizziness and somnolence. Other
reasons for discontinuation from the trials, occurring with greater frequency in the LYRICA
group than in the placebo group, were asthenia, confusion, and peripheral edema. Each of these
events led to withdrawal in approximately 1% of patients.
Most Common Adverse Reactions
Table 3 lists all adverse reactions, regardless of causality, occurring in ≥1% of patients with
neuropathic pain associated with diabetic neuropathy in the combined LYRICA group for which
the incidence was greater in this combined LYRICA group than in the placebo group. A majority
of pregabalin-treated patients in clinical studies had adverse reactions with a maximum intensity
of "mild" or "moderate”.
Table 3. Treatment-emergent adverse reaction incidence in controlled trials in
neuropathic pain associated with diabetic peripheral neuropathy (events in at
least 1% of all LYRICA-treated patients and at least numerically more in all
LYRICA than in the placebo group)
Body system
Preferred term
Body as a whole
Asthenia
Accidental injury
Back pain
Chest pain
Face edema
Digestive system
Dry mouth
Constipation
Flatulence
Metabolic and
nutritional disorders
Peripheral edema
Weight gain
Edema
Hypoglycemia
Nervous system
Dizziness
Somnolence
Neuropathy
Ataxia
Vertigo
Confusion
Euphoria
Incoordination
Thinking abnormal†
Tremor
Abnormal gait
Amnesia
Nervousness
75
mg/day
[N=77]
%
150
mg/day
[N=212]
%
300
mg/day
[N=321]
%
600
mg/day
[N=369]
%
4
5
0
4
0
2
2
2
1
1
4
2
1
1
1
3
0
3
2
2
0
4
0
0
1
8
4
9
6
1
0
0
1
1
1
1
3
0
All PGB* Placebo
[N=979]
%
[N=459]
%
7
6
2
2
2
5
4
2
2
1
2
3
0
1
0
5
4
2
7
6
3
5
4
2
1
2
1
6
4
2
3
9
4
4
2
12
6
2
1
9
4
2
2
2
0
0
1
9
6
2
1
2
1
0
0
0
1
0
1
1
23
13
2
2
2
2
3
2
1
1
1
0
1
29
16
5
4
4
3
2
2
3
2
3
2
1
21
12
4
3
3
2
2
2
2
1
1
1
1
5
3
3
1
1
1
0
0
0
0
0
0
0
Respiratory system
Dyspnea
Special senses
Blurry vision‡
Abnormal vision
3
0
2
2
2
1
3
1
1
0
3
1
6
1
4
1
2
0
* PGB: pregabalin
†
Thinking abnormal primarily consists of events related to difficulty with concentration/attention
but also includes events related to cognition and language problems and slowed thinking.
‡
Investigator term; summary level term is amblyopia
Controlled Studies in Postherpetic Neuralgia
Adverse Reactions Leading to Discontinuation
In clinical trials in patients with postherpetic neuralgia, 14% of patients treated with LYRICA
and 7% of patients treated with placebo discontinued prematurely due to adverse reactions. In the
LYRICA treatment group, the most common reasons for discontinuation due to adverse reactions
were dizziness (4%) and somnolence (3%). In comparison, less than 1% of placebo patients
withdrew due to dizziness and somnolence. Other reasons for discontinuation from the trials,
occurring in greater frequency in the LYRICA group than in the placebo group, were confusion
(2%), as well as peripheral edema, asthenia, ataxia, and abnormal gait (1% each).
Most Common Adverse Reactions
Table 4 lists all adverse reactions, regardless of causality, occurring in ≥ 1% of patients with
neuropathic pain associated with postherpetic neuralgia in the combined LYRICA group for
which the incidence was greater in this combined LYRICA group than in the placebo group. In
addition, an event is included, even if the incidence in the all LYRICA group is not greater than
in the placebo group, if the incidence of the event in the 600 mg/day group is more than twice
that in the placebo group. A majority of pregabalin-treated patients in clinical studies had
adverse reactions with a maximum intensity of "mild" or "moderate”. Overall, 12.4% of all
pregabalin-treated patients and 9.0% of all placebo-treated patients had at least one severe event
while 8% of pregabalin-treated patients and 4.3% of placebo-treated patients had at least one
severe treatment-related adverse event.
Table 4. Treatment-emergent adverse reaction incidence in controlled trials in
neuropathic pain associated with postherpetic neuralgia (events in at least 1%
of all LYRICA-treated patients and at least numerically more in all LYRICA
than in the placebo group)
Body system
Preferred term
Body as a whole
Infection
Headache
Pain
Accidental injury
Flu syndrome
75 mg/d 150 mg/d 300 mg/d 600 mg/d All PGB*
[N=84] [N=302] [N=312] [N=154] [N=852]
%
%
%
%
%
14
5
5
4
1
8
9
4
3
2
6
5
5
3
2
3
8
5
5
1
7
7
5
3
2
Placebo
[N=398]
%
4
5
4
2
1
Face edema
Digestive system
Dry mouth
Constipation
Flatulence
Vomiting
Metabolic and
nutritional disorders
Peripheral edema
Weight gain
Edema
Musculoskeletal system
Myasthenia
Nervous system
Dizziness
Somnolence
Ataxia
Abnormal gait
Confusion
Thinking abnormal†
Incoordination
Amnesia
Speech disorder
Respiratory system
Bronchitis
Special senses
Blurry vision‡
Diplopia
Abnormal vision
Eye Disorder
Urogenital System
Urinary Incontinence
0
2
1
3
2
1
7
4
2
1
7
5
1
1
6
5
2
3
15
5
3
3
8
5
2
2
3
2
1
1
0
1
0
8
2
1
16
5
2
16
7
6
12
4
2
4
0
1
1
1
1
1
1
0
11
8
1
0
1
0
2
0
0
18
12
2
2
2
2
2
1
0
31
18
5
4
3
1
1
1
1
37
25
9
8
7
6
3
4
3
26
16
5
4
3
2
2
2
1
9
5
1
1
0
2
0
0
0
0
1
1
3
1
1
1
0
0
0
5
2
1
1
5
2
2
1
9
4
5
2
5
2
2
1
3
0
0
0
0
1
1
2
1
0
* PGB: pregabalin
†
Thinking abnormal primarily consists of events related to difficulty with
concentration/attention but also includes events related to cognition and language
problems and slowed thinking.
‡
Investigator term; summary level term is amblyopia
Controlled Add-On Studies in Adjunctive Therapy for Adult Patients with Partial Onset Seizures
Adverse Reactions Leading to Discontinuation
Approximately 15% of patients receiving LYRICA and 6% of patients receiving placebo in addon epilepsy trials discontinued prematurely due to adverse reactions. In the LYRICA treatment
group, the adverse reactions most frequently leading to discontinuation were dizziness (6%),
ataxia (4%), and somnolence (3%). In comparison, <1% of patients in the placebo group
withdrew due to each of these events. Other adverse reactions that led to discontinuation of at
least 1% of patients in the LYRICA group and at least twice as frequently compared to the
placebo group were asthenia, diplopia, blurred vision, thinking abnormal, nausea, tremor,
vertigo, headache, and confusion (which each led to withdrawal in 2% or less of patients).
Most Common Adverse Reactions
Table 5 lists all dose-related adverse reactions occurring in at least 2% of all LYRICA-treated
patients. Dose-relatedness was defined as the incidence of the adverse event in the 600 mg/day
group was at least 2% greater than the rate in both the placebo and 150 mg/day groups. In these
studies, 758 patients received LYRICA and 294 patients received placebo for up to 12 weeks.
Because patients were also treated with 1 to 3 other AEDs, it is not possible to determine
whether the following adverse reactions can be ascribed to LYRICA alone, or the combination of
LYRICA and other AEDs. A majority of pregabalin-treated patients in clinical studies had
adverse reactions with a maximum intensity of "mild" or "moderate”.
Table 5. Dose-related treatment-emergent adverse reaction incidence in controlled
trials in adjunctive therapy for adult patients with partial onset seizures (events in
at least 2% of all LYRICA-treated patients and the adverse reaction in the 600
mg/day group was ≥2% the rate in both the placebo and 150 mg/day groups)
Body System
Preferred Term
150 mg/d
300 mg/d
600 mg/d
All PGB*
Placebo
[N = 185]
%
[N = 90]
%
[N = 395]
%
[N = 670]†
%
[N = 294]
%
11
2
10
5
9
4
5
3
3
2
1
6
6
7
5
4
4
1
1
2
7
3
16
6
12
5
1
2
31
18
10
7
8
2
2
3
3
4
2
0
38
28
20
11
9
6
7
6
5
5
5
4
32
22
15
8
8
5
5
4
4
4
4
2
11
11
4
4
2
2
1
1
0
1
2
0
Body as a Whole
Accidental Injury
7
Pain
3
Digestive System
Increased Appetite
2
Dry Mouth
1
Constipation
1
Metabolic and Nutritional Disorders
Weight Gain
5
Peripheral Edema
3
Nervous System
Dizziness
18
Somnolence
11
Ataxia
6
Tremor
3
Thinking Abnormal‡
4
Amnesia
3
Speech Disorder
1
Incoordination
1
Abnormal Gait
1
Twitching
0
Confusion
1
Myoclonus
1
Special Senses
Blurred Vision§
Diplopia
Abnormal Vision
5
5
3
8
7
1
12
12
5
10
9
4
4
4
1
* PGB: pregabalin
†
Excludes patients who received the 50 mg dose in Study E1.
‡
Thinking abnormal primarily consists of events related to difficulty with concentration/attention but also
includes events related to cognition and language problems and slowed thinking.
§
Investigator term; summary level term is amblyopia.
Controlled Studies with Fibromyalgia
Adverse Reactions Leading to Discontinuation
In clinical trials of patients with fibromyalgia, 19% of patients treated with pregabalin (150–600
mg/day) and 10% of patients treated with placebo discontinued prematurely due to adverse
reactions. In the pregabalin treatment group, the most common reasons for discontinuation due to
adverse reactions were dizziness (6%) and somnolence (3%). In comparison, <1% of placebotreated patients withdrew due to dizziness and somnolence. Other reasons for discontinuation
from the trials, occurring with greater frequency in the pregabalin treatment group than in the
placebo treatment group, were fatigue, headache, balance disorder, and weight increased. Each
of these adverse reactions led to withdrawal in approximately 1% of patients.
Most Common Adverse Reactions
Table 6 lists all adverse reactions, regardless of causality, occurring in ≥2% of patients with
fibromyalgia in the ‘all pregabalin’ treatment group for which the incidence was greater than in
the placebo treatment group. A majority of pregabalin-treated patients in clinical studies
experienced adverse reactions with a maximum intensity of "mild" or "moderate".
Table 6. Treatment-emergent adverse reaction incidence in controlled trials in
fibromyalgia (events) in at least 2% of all LYRICA-treated patients and
occurring more frequently in the all pregabalin-group than in the placebo
treatment group)
System Organ Class
Preferred term
Ear and Labyrinth
Disorders
Vertigo
Eye Disorders
Vision blurred
Gastrointestinal
Disorders
Dry mouth
Constipation
Vomiting
Flatulence
150
300
450
600
All PGB*
mg/d
mg/d
mg/d
mg/d
[N=132] [N=502] [N=505] [N=378] [N=1517]
%
%
%
%
%
Placebo
[N=505]
%
2
2
2
1
2
0
8
7
7
12
8
1
7
4
2
1
6
4
3
1
9
7
3
2
9
10
2
2
8
7
3
2
2
2
2
1
Abdominal distension
General Disorders and
Administrative Site
Conditions
Fatigue
Edema peripheral
Chest pain
Feeling abnormal
Edema
Feeling drunk
Infections and
Infestations
Sinusitis
Investigations
Weight increased
Metabolism and
Nutrition Disorders
Increased appetite
Fluid retention
Musculoskeletal and
Connective Tissue
Disorders
Arthralgia
Muscle spasms
Back pain
Nervous System
Disorders
Dizziness
Somnolence
Headache
Disturbance in attention
Balance disorder
Memory impairment
Coordination abnormal
Hypoesthesia
Lethargy
Tremor
Psychiatric Disorders
Euphoric Mood
Confusional state
Anxiety
Disorientation
Depression
Respiratory, Thoracic
and Mediastinal Disorders
Pharyngolaryngeal pain
* PGB: pregabalin
2
2
2
2
2
1
5
5
2
1
1
1
7
5
1
3
2
2
6
6
1
2
1
1
8
9
2
2
2
2
7
6
2
2
2
2
4
2
1
0
1
0
4
5
7
5
5
4
8
10
10
14
11
2
4
2
3
3
5
3
7
2
5
2
1
1
4
2
2
3
4
3
3
4
4
6
4
3
4
4
3
2
2
3
23
13
11
4
2
1
2
2
2
0
31
18
12
4
3
3
1
2
2
1
43
22
14
6
6
4
2
3
1
3
45
22
10
6
9
4
2
2
2
2
38
20
12
5
5
3
2
2
2
2
9
4
12
1
0
0
1
1
0
0
2
0
2
1
2
5
2
2
0
2
6
3
2
2
2
7
4
2
1
2
6
3
2
2
2
1
0
1
0
2
2
1
3
3
2
2
Controlled Studies in Neuropathic Pain Associated with Spinal Cord Injury
Adverse Reactions Leading to Discontinuation
In clinical trials of patients with neuropathic pain associated with spinal cord injury, 13% of
patients treated with pregabalin and 10% of patients treated with placebo discontinued
prematurely due to adverse reactions. In the pregabalin treatment group, the most common
reasons for discontinuation due to adverse reactions were somnolence (3%) and edema (2%). In
comparison, none of the placebo-treated patients withdrew due to somnolence and edema. Other
reasons for discontinuation from the trials, occurring with greater frequency in the pregabalin
treatment group than in the placebo treatment group, were fatigue and balance disorder. Each of
these adverse reactions led to withdrawal in less than 2% of patients.
Most Common Adverse Reactions
Table 7 lists all adverse reactions, regardless of causality, occurring in 2% of patients with
neuropathic pain associated with spinal cord injury in the controlled trials. A majority of
pregabalin-treated patients in clinical studies experienced adverse reactions with a maximum
intensity of "mild" or "moderate".
Table 7. Treatment-emergent adverse reaction incidence in controlled trials in neuropathic pain
associated with spinal cord injury (events in at least 2% of all LYRICA-treated patients and occurring
more frequently in the all pregabalin-group than in the placebo treatment group)
System Organ Class
Preferred term
Ear and labryrinth disorders
Vertigo
Eye disorders
Vision blurred
Gastrointestinal disorders
Dry mouth
Constipation
Nausea
Vomiting
General disorders and
administration site conditions
Fatigue
Edema peripheral
Edema
Pain
Infections and infestations
Nasopharyngitis
Investigations
Weight increased
Blood creatine phosphokinase increased
Musculoskeletal and
connective tissue disorders
Muscular weakness
Pain in extremity
Neck pain
PGB* (N=182)
%
Placebo (N=174)
%
2.7
1.1
6.6
1.1
11.0
8.2
4.9
2.7
2.9
5.7
4.0
1.1
11.0
10.4
8.2
3.3
4.0
5.2
1.1
1.1
8.2
4.6
3.3
2.7
1.1
0
4.9
3.3
2.7
1.7
2.3
1.1
Back pain
Joint swelling
Nervous system disorders
Somnolence
Dizziness
Disturbance in attention
Memory impairment
Paresthesia
Psychiatric disorders
Insomnia
Euphoric mood
Renal and urinary disorders
Urinary incontinence
Skin and subcutaneous tissue disorders
Decubitus ulcer
Vascular disorders
Hypertension
Hypotension
2.2
2.2
1.7
0
35.7
20.9
3.8
3.3
2.2
11.5
6.9
0
1.1
0.6
3.8
2.2
2.9
0.6
2.7
1.1
2.7
1.1
2.2
2.2
1.1
0
* PGB: Pregabalin
Other Adverse Reactions Observed During the Clinical Studies of LYRICA
Following is a list of treatment-emergent adverse reactions reported by patients treated with
LYRICA during all clinical trials. The listing does not include those events already listed in the
previous tables or elsewhere in labeling, those events for which a drug cause was remote, those
events which were so general as to be uninformative, and those events reported only once which
did not have a substantial probability of being acutely life-threatening.
Events are categorized by body system and listed in order of decreasing frequency according to
the following definitions: frequent adverse reactions are those occurring on one or more
occasions in at least 1/100 patients; infrequent adverse reactions are those occurring in 1/100 to
1/1000 patients; rare reactions are those occurring in fewer than 1/1000 patients. Events of major
clinical importance are described in the Warnings and Precautions section (5).
Body as a Whole – Frequent: Abdominal pain, Allergic reaction, Fever, Infrequent: Abscess,
Cellulitis, Chills, Malaise, Neck rigidity, Overdose, Pelvic pain, Photosensitivity reaction, Rare:
Anaphylactoid reaction, Ascites, Granuloma, Hangover effect, Intentional Injury,
Retroperitoneal Fibrosis, Shock
Cardiovascular System – Infrequent: Deep thrombophlebitis, Heart failure, Hypotension,
Postural hypotension, Retinal vascular disorder, Syncope; Rare: ST Depressed, Ventricular
Fibrillation
Digestive System – Frequent: Gastroenteritis, Increased appetite; Infrequent: Cholecystitis,
Cholelithiasis, Colitis, Dysphagia, Esophagitis, Gastritis, Gastrointestinal hemorrhage, Melena,
Mouth ulceration, Pancreatitis, Rectal hemorrhage, Tongue edema; Rare: Aphthous stomatitis,
Esophageal Ulcer, Periodontal abscess
Hemic and Lymphatic System – Frequent: Ecchymosis; Infrequent: Anemia, Eosinophilia,
Hypochromic anemia, Leukocytosis, Leukopenia, Lymphadenopathy, Thrombocytopenia; Rare:
Myelofibrosis, Polycythemia, Prothrombin decreased, Purpura, Thrombocythemia
Metabolic and Nutritional Disorders – Rare: Glucose Tolerance Decreased, Urate Crystalluria
Musculoskeletal System – Frequent: Arthralgia, Leg cramps, Myalgia, Myasthenia; Infrequent:
Arthrosis; Rare: Chondrodystrophy, Generalized Spasm
Nervous System – Frequent: Anxiety, Depersonalization, Hypertonia, Hypoesthesia, Libido
decreased, Nystagmus, Paresthesia, Sedation, Stupor, Twitching; Infrequent: Abnormal dreams,
Agitation, Apathy, Aphasia, Circumoral paresthesia, Dysarthria, Hallucinations, Hostility,
Hyperalgesia, Hyperesthesia, Hyperkinesia, Hypokinesia, Hypotonia, Libido increased,
Myoclonus, Neuralgia, Rare: Addiction, Cerebellar syndrome, Cogwheel rigidity, Coma,
Delirium, Delusions, Dysautonomia, Dyskinesia, Dystonia, Encephalopathy, Extrapyramidal
syndrome, Guillain-Barré syndrome, Hypalgesia, Intracranial hypertension, Manic reaction,
Paranoid reaction, Peripheral neuritis, Personality disorder, Psychotic depression, Schizophrenic
reaction, Sleep disorder, Torticollis, Trismus
Respiratory System – Rare: Apnea, Atelectasis, Bronchiolitis, Hiccup, Laryngismus, Lung
edema, Lung fibrosis, Yawn
Skin and Appendages – Frequent: Pruritus, Infrequent: Alopecia, Dry skin, Eczema, Hirsutism,
Skin ulcer, Urticaria, Vesiculobullous rash; Rare: Angioedema, Exfoliative dermatitis, Lichenoid
dermatitis, Melanosis, Nail Disorder, Petechial rash, Purpuric rash, Pustular rash, Skin atrophy,
Skin necrosis, Skin nodule, Stevens-Johnson syndrome, Subcutaneous nodule
Special senses – Frequent: Conjunctivitis, Diplopia, Otitis media, Tinnitus; Infrequent:
Abnormality of accommodation, Blepharitis, Dry eyes, Eye hemorrhage, Hyperacusis,
Photophobia, Retinal edema, Taste loss, Taste perversion; Rare: Anisocoria, Blindness, Corneal
ulcer, Exophthalmos, Extraocular palsy, Iritis, Keratitis, Keratoconjunctivitis, Miosis, Mydriasis,
Night blindness, Ophthalmoplegia, Optic atrophy, Papilledema, Parosmia, Ptosis, Uveitis
Urogenital System – Frequent: Anorgasmia, Impotence, Urinary frequency, Urinary
incontinence; Infrequent: Abnormal ejaculation, Albuminuria, Amenorrhea, Dysmenorrhea,
Dysuria, Hematuria, Kidney calculus, Leukorrhea, Menorrhagia, Metrorrhagia, Nephritis,
Oliguria, Urinary retention, Urine abnormality; Rare: Acute kidney failure, Balanitis, Bladder
Neoplasm, Cervicitis, Dyspareunia, Epididymitis, Female lactation, Glomerulitis, Ovarian
disorder, Pyelonephritis
Comparison of Gender and Race
The overall adverse event profile of pregabalin was similar between women and men. There are
insufficient data to support a statement regarding the distribution of adverse experience reports
by race.
6.2 Post-marketing Experience
The following adverse reactions have been identified during postapproval use of LYRICA.
Because these reactions are reported voluntarily from a population of uncertain size, it is not
always possible to reliably estimate their frequency or establish a causal relationship to drug
exposure.
Nervous System Disorders – Headache
Gastrointestinal Disorders – Nausea, Diarrhea
Reproductive System and Breast Disorders – Gynecomastia, Breast Enlargement
In addition, there are post-marketing reports of events related to reduced lower gastrointestinal
tract function (e.g., intestinal obstruction, paralytic ileus, constipation) when LYRICA was coadministered with medications that have the potential to produce constipation, such as opioid
analgesics. There are also post-marketing reports of respiratory failure and coma in patients
taking pregabalin and other CNS depressant medications.
7 DRUG INTERACTIONS
Since LYRICA is predominantly excreted unchanged in the urine, undergoes negligible
metabolism in humans (<2% of a dose recovered in urine as metabolites), and does not bind to
plasma proteins, its pharmacokinetics are unlikely to be affected by other agents through
metabolic interactions or protein binding displacement. In vitro and in vivo studies showed that
LYRICA is unlikely to be involved in significant pharmacokinetic drug interactions.
Specifically, there are no pharmacokinetic interactions between pregabalin and the following
antiepileptic drugs: carbamazepine, valproic acid, lamotrigine, phenytoin, phenobarbital, and
topiramate. Important pharmacokinetic interactions would also not be expected to occur between
LYRICA and commonly used antiepileptic drugs [see Clinical Pharmacology (12)].
Pharmacodynamics
Multiple oral doses of LYRICA were co-administered with oxycodone, lorazepam, or ethanol.
Although no pharmacokinetic interactions were seen, additive effects on cognitive and gross
motor functioning were seen when LYRICA was co-administered with these drugs. No clinically
important effects on respiration were seen.
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Pregnancy Category C. Increased incidences of fetal structural abnormalities and other
manifestations of developmental toxicity, including lethality, growth retardation, and nervous
and reproductive system functional impairment, were observed in the offspring of rats and
rabbits given pregabalin during pregnancy, at doses that produced plasma pregabalin exposures
(AUC) ≥5 times human exposure at the maximum recommended dose (MRD) of 600 mg/day.
When pregnant rats were given pregabalin (500, 1250, or 2500 mg/kg) orally throughout the
period of organogenesis, incidences of specific skull alterations attributed to abnormally
advanced ossification (premature fusion of the jugal and nasal sutures) were increased at ≥1250
mg/kg, and incidences of skeletal variations and retarded ossification were increased at all doses.
Fetal body weights were decreased at the highest dose. The low dose in this study was associated
with a plasma exposure (AUC) approximately 17 times human exposure at the MRD of 600
mg/day. A no-effect dose for rat embryo-fetal developmental toxicity was not established.
When pregnant rabbits were given LYRICA (250, 500, or 1250 mg/kg) orally throughout the
period of organogenesis, decreased fetal body weight and increased incidences of skeletal
malformations, visceral variations, and retarded ossification were observed at the highest dose.
The no-effect dose for developmental toxicity in rabbits (500 mg/kg) was associated with a
plasma exposure approximately 16 times human exposure at the MRD.
In a study in which female rats were dosed with LYRICA (50, 100, 250, 1250, or 2500 mg/kg)
throughout gestation and lactation, offspring growth was reduced at ≥ 100 mg/kg and offspring
survival was decreased at ≥250 mg/kg. The effect on offspring survival was pronounced at doses
≥1250 mg/kg, with 100% mortality in high-dose litters. When offspring were tested as adults,
neurobehavioral abnormalities (decreased auditory startle responding) were observed at ≥250
mg/kg and reproductive impairment (decreased fertility and litter size) was seen at 1250 mg/kg.
The no-effect dose for pre- and postnatal developmental toxicity in rats (50 mg/kg) produced a
plasma exposure approximately 2 times human exposure at the MRD.
There are no adequate and well-controlled studies in pregnant women. Use LYRICA during
pregnancy only if the potential benefit justifies the potential risk to the fetus.
To provide information regarding the effects of in utero exposure to LYRICA, physicians are
advised to recommend that pregnant patients taking LYRICA enroll in the North American
Antiepileptic Drug (NAAED) Pregnancy Registry. This can be done by calling the toll free
number 1-888-233-2334, and must be done by patients themselves. Information on the registry
can also be found at the website http://www.aedpregnancyregistry.org/.
8.2 Labor and Delivery
The effects of LYRICA on labor and delivery in pregnant women are unknown. In the prenatalpostnatal study in rats, pregabalin prolonged gestation and induced dystocia at exposures ≥50
times the mean human exposure (AUC (0–24) of 123 µg·hr/mL) at the maximum recommended
clinical dose of 600 mg/day.
8.3 Nursing Mothers
It is not known if pregabalin is excreted in human milk; it is, however, present in the milk of rats.
Because many drugs are excreted in human milk, and because of the potential for tumorigenicity
shown for pregabalin in animal studies, decide whether to discontinue nursing or to discontinue
the drug, taking into account the importance of the drug to the mother.
8.4 Pediatric Use
The safety and efficacy of pregabalin in pediatric patients have not been established.
In studies in which pregabalin (50 to 500 mg/kg) was orally administered to young rats from
early in the postnatal period (Postnatal Day 7) through sexual maturity, neurobehavioral
abnormalities (deficits in learning and memory, altered locomotor activity, decreased auditory
startle responding and habituation) and reproductive impairment (delayed sexual maturation and
decreased fertility in males and females) were observed at doses ≥50 mg/kg. The
neurobehavioral changes of acoustic startle persisted at ≥250 mg/kg and locomotor activity and
water maze performance at ≥500 mg/kg in animals tested after cessation of dosing and, thus,
were considered to represent long-term effects. The low effect dose for developmental
neurotoxicity and reproductive impairment in juvenile rats (50 mg/kg) was associated with a
plasma pregabalin exposure (AUC) approximately equal to human exposure at the maximum
recommended dose of 600 mg/day. A no-effect dose was not established.
8.5 Geriatric Use
In controlled clinical studies of LYRICA in neuropathic pain associated with diabetic peripheral
neuropathy, 246 patients were 65 to 74 years of age, and 73 patients were 75 years of age or
older.
In controlled clinical studies of LYRICA in neuropathic pain associated with postherpetic
neuralgia, 282 patients were 65 to 74 years of age, and 379 patients were 75 years of age or
older.
In controlled clinical studies of LYRICA in epilepsy, there were only 10 patients 65 to 74 years
of age, and 2 patients who were 75 years of age or older.
No overall differences in safety and efficacy were observed between these patients and younger
patients.
In controlled clinical studies of LYRICA in fibromyalgia, 106 patients were 65 years of age or
older. Although the adverse reaction profile was similar between the two age groups, the
following neurological adverse reactions were more frequent in patients 65 years of age or older:
dizziness, vision blurred, balance disorder, tremor, confusional state, coordination abnormal, and
lethargy.
LYRICA is known to be substantially excreted by the kidney, and the risk of toxic reactions to
LYRICA may be greater in patients with impaired renal function. Because LYRICA is
eliminated primarily by renal excretion, adjust the dose for elderly patients with renal
impairment [see Dosage and Administration (2.6)].
9 DRUG ABUSE AND DEPENDENCE
9.1 Controlled Substance
LYRICA is a Schedule V controlled substance.
LYRICA is not known to be active at receptor sites associated with drugs of abuse. As with any
CNS active drug, carefully evaluate patients for history of drug abuse and observe them for signs
of LYRICA misuse or abuse (e.g., development of tolerance, dose escalation, drug-seeking
behavior).
9.2 Abuse
In a study of recreational users (N=15) of sedative/hypnotic drugs, including alcohol, LYRICA
(450 mg, single dose) received subjective ratings of "good drug effect," "high" and "liking" to a
degree that was similar to diazepam (30 mg, single dose). In controlled clinical studies in over
5500 patients, 4 % of LYRICA-treated patients and 1 % of placebo-treated patients overall
reported euphoria as an adverse reaction, though in some patient populations studied, this
reporting rate was higher and ranged from 1 to 12%.
9.3 Dependence
In clinical studies, following abrupt or rapid discontinuation of LYRICA, some patients reported
symptoms including insomnia, nausea, headache or diarrhea [see Warnings and Precautions
(5.8)], consistent with physical dependence. In the postmarketing experience, in addition to these
reported symptoms there have also been reported cases of anxiety and hyperhidrosis.
10 OVERDOSAGE
Signs, Symptoms and Laboratory Findings of Acute Overdosage in Humans
There is limited experience with overdose of LYRICA. The highest reported accidental overdose
of LYRICA during the clinical development program was 8000 mg, and there were no notable
clinical consequences.
Treatment or Management of Overdose
There is no specific antidote for overdose with LYRICA. If indicated, elimination of unabsorbed
drug may be attempted by emesis or gastric lavage; observe usual precautions to maintain the
airway. General supportive care of the patient is indicated including monitoring of vital signs and
observation of the clinical status of the patient. Contact a Certified Poison Control Center for upto-date information on the management of overdose with LYRICA.
Although hemodialysis has not been performed in the few known cases of overdose, it may be
indicated by the patient's clinical state or in patients with significant renal impairment. Standard
hemodialysis procedures result in significant clearance of pregabalin (approximately 50% in 4
hours).
11 DESCRIPTION
Pregabalin is described chemically as (S)-3-(aminomethyl)-5-methylhexanoic acid. The
molecular formula is C8H17NO2 and the molecular weight is 159.23. The chemical structure of
pregabalin is:
Pregabalin is a white to off-white, crystalline solid with a pKa1 of 4.2 and a pKa2 of 10.6. It is
freely soluble in water and both basic and acidic aqueous solutions. The log of the partition
coefficient (n-octanol/0.05M phosphate buffer) at pH 7.4 is – 1.35.
LYRICA (pregabalin) Capsules are administered orally and are supplied as imprinted hard-shell
capsules containing 25, 50, 75, 100, 150, 200, 225, and 300 mg of pregabalin, along with lactose
monohydrate, cornstarch, and talc as inactive ingredients. The capsule shells contain gelatin and
titanium dioxide. In addition, the orange capsule shells contain red iron oxide and the white
capsule shells contain sodium lauryl sulfate and colloidal silicon dioxide. Colloidal silicon
dioxide is a manufacturing aid that may or may not be present in the capsule shells. The
imprinting ink contains shellac, black iron oxide, propylene glycol, and potassium hydroxide.
LYRICA (pregabalin) oral solution, 20 mg/mL, is administered orally and is supplied as a clear,
colorless solution contained in a 16 fluid ounce white HDPE bottle with a polyethylene-lined
closure. The oral solution contains 20 mg/mL of pregabalin, along with methylparaben,
propylparaben, monobasic sodium phosphate anhydrous, dibasic sodium phosphate anhydrous,
sucralose, artificial strawberry #11545 and purified water as inactive ingredients.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
LYRICA (pregabalin) binds with high affinity to the alpha2-delta site (an auxiliary subunit of
voltage-gated calcium channels) in central nervous system tissues. Although the mechanism of
action of pregabalin has not been fully elucidated, results with genetically modified mice and
with compounds structurally related to pregabalin (such as gabapentin) suggest that binding to
the alpha2-delta subunit may be involved in pregabalin's anti-nociceptive and antiseizure effects
in animals. In animal models of nerve damage, pregabalin has been shown to reduce calciumdependent release of pro-nociceptive neurotransmitters in the spinal cord, possibly by disrupting
alpha2-delta containing-calcium channel trafficking and/or reducing calcium currents. Evidence
from other animal models of nerve damage and persistent pain suggest the anti-nociceptive
activities of pregabalin may also be mediated through interactions with descending noradrenergic
and serotonergic pathways originating from the brainstem that modulate pain transmission in the
spinal cord.
While pregabalin is a structural derivative of the inhibitory neurotransmitter gammaaminobutyric acid (GABA), it does not bind directly to GABAA, GABAB, or benzodiazepine
receptors, does not augment GABAA responses in cultured neurons, does not alter rat brain
GABA concentration or have acute effects on GABA uptake or degradation. However, in
cultured neurons prolonged application of pregabalin increases the density of GABA transporter
protein and increases the rate of functional GABA transport. Pregabalin does not block sodium
channels, is not active at opiate receptors, and does not alter cyclooxygenase enzyme activity. It
is inactive at serotonin and dopamine receptors and does not inhibit dopamine, serotonin, or
noradrenaline reuptake.
12.3 Pharmacokinetics
Pregabalin is well absorbed after oral administration, is eliminated largely by renal excretion,
and has an elimination half-life of about 6 hours.
Absorption and Distribution
Following oral administration of LYRICA capsules under fasting conditions, peak plasma
concentrations occur within 1.5 hours. Pregabalin oral bioavailability is ≥90% and is independent
of dose. Following single- (25 to 300 mg) and multiple- dose (75 to 900 mg/day) administration,
maximum plasma concentrations (Cmax) and area under the plasma concentration-time curve
(AUC) values increase linearly. Following repeated administration, steady state is achieved
within 24 to 48 hours. Multiple-dose pharmacokinetics can be predicted from single-dose data.
The rate of pregabalin absorption is decreased when given with food, resulting in a decrease in
Cmax of approximately 25% to 30% and an increase in Tmax to approximately 3 hours. However,
administration of pregabalin with food has no clinically relevant effect on the total absorption of
pregabalin. Therefore, pregabalin can be taken with or without food.
Pregabalin does not bind to plasma proteins. The apparent volume of distribution of pregabalin
following oral administration is approximately 0.5 L/kg. Pregabalin is a substrate for system L
transporter which is responsible for the transport of large amino acids across the blood brain
barrier. Although there are no data in humans, pregabalin has been shown to cross the blood
brain barrier in mice, rats, and monkeys. In addition, pregabalin has been shown to cross the
placenta in rats and is present in the milk of lactating rats.
Metabolism and Elimination
Pregabalin undergoes negligible metabolism in humans. Following a dose of radiolabeled
pregabalin, approximately 90% of the administered dose was recovered in the urine as
unchanged pregabalin. The N-methylated derivative of pregabalin, the major metabolite of
pregabalin found in urine, accounted for 0.9% of the dose. In preclinical studies, pregabalin (Senantiomer) did not undergo racemization to the R-enantiomer in mice, rats, rabbits, or monkeys.
Pregabalin is eliminated from the systemic circulation primarily by renal excretion as unchanged
drug with a mean elimination half-life of 6.3 hours in subjects with normal renal function. Mean
renal clearance was estimated to be 67.0 to 80.9 mL/min in young healthy subjects. Because
pregabalin is not bound to plasma proteins this clearance rate indicates that renal tubular
reabsorption is involved. Pregabalin elimination is nearly proportional to creatinine clearance
(CLcr) [see Dosage and Administration, (2.6)].
Pharmacokinetics in Special Populations
Race
In population pharmacokinetic analyses of the clinical studies in various populations, the
pharmacokinetics of LYRICA were not significantly affected by race (Caucasians, Blacks, and
Hispanics).
Gender
Population pharmacokinetic analyses of the clinical studies showed that the relationship between
daily dose and LYRICA drug exposure is similar between genders.
Renal Impairment and Hemodialysis
Pregabalin clearance is nearly proportional to creatinine clearance (CLcr). Dosage reduction in
patients with renal dysfunction is necessary. Pregabalin is effectively removed from plasma by
hemodialysis. Following a 4-hour hemodialysis treatment, plasma pregabalin concentrations are
reduced by approximately 50%. For patients on hemodialysis, dosing must be modified [see
Dosage and Administration (2.6)].
Elderly
Pregabalin oral clearance tended to decrease with increasing age. This decrease in pregabalin
oral clearance is consistent with age-related decreases in CLcr. Reduction of pregabalin dose
may be required in patients who have age-related compromised renal function [see Dosage and
Administration, (2.6)].
Pediatric Pharmacokinetics
Pharmacokinetics of pregabalin have not been adequately studied in pediatric patients.
Drug Interactions
In Vitro Studies
Pregabalin, at concentrations that were, in general, 10-times those attained in clinical trials, does
not inhibit human CYP1A2, CYP2A6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4
enzyme systems. In vitro drug interaction studies demonstrate that pregabalin does not induce
CYP1A2 or CYP3A4 activity. Therefore, an increase in the metabolism of coadministered
CYP1A2 substrates (e.g. theophylline, caffeine) or CYP 3A4 substrates (e.g., midazolam,
testosterone) is not anticipated.
In Vivo Studies
The drug interaction studies described in this section were conducted in healthy adults, and
across various patient populations.
Gabapentin
The pharmacokinetic interactions of pregabalin and gabapentin were investigated in 12 healthy
subjects following concomitant single-dose administration of 100-mg pregabalin and 300-mg
gabapentin and in 18 healthy subjects following concomitant multiple-dose administration of
200-mg pregabalin every 8 hours and 400-mg gabapentin every 8 hours. Gabapentin
pharmacokinetics following single- and multiple-dose administration were unaltered by
pregabalin coadministration. The extent of pregabalin absorption was unaffected by gabapentin
coadministration, although there was a small reduction in rate of absorption.
Oral Contraceptive
Pregabalin coadministration (200 mg three times a day) had no effect on the steady-state
pharmacokinetics of norethindrone and ethinyl estradiol (1 mg/35 µg, respectively) in healthy
subjects.
Lorazepam
Multiple-dose administration of pregabalin (300 mg twice a day) in healthy subjects had no
effect on the rate and extent of lorazepam single-dose pharmacokinetics and single-dose
administration of lorazepam (1 mg) had no effect on the steady-state pharmacokinetics of
pregabalin.
Oxycodone
Multiple-dose administration of pregabalin (300 mg twice a day) in healthy subjects had no
effect on the rate and extent of oxycodone single-dose pharmacokinetics. Single-dose
administration of oxycodone (10 mg) had no effect on the steady-state pharmacokinetics of
pregabalin.
Ethanol
Multiple-dose administration of pregabalin (300 mg twice a day) in healthy subjects had no
effect on the rate and extent of ethanol single-dose pharmacokinetics and single-dose
administration of ethanol (0.7 g/kg) had no effect on the steady-state pharmacokinetics of
pregabalin.
Phenytoin, carbamazepine, valproic acid, and lamotrigine
Steady-state trough plasma concentrations of phenytoin, carbamazepine and carbamazepine
10,11 epoxide, valproic acid, and lamotrigine were not affected by concomitant pregabalin (200
mg three times a day) administration.
Population pharmacokinetic analyses in patients treated with pregabalin and various concomitant
medications suggest the following:
Therapeutic class
Specific concomitant drug studied
Concomitant drug has no effect on the pharmacokinetics of pregabalin
Hypoglycemics
Glyburide, insulin, metformin
Diuretics
Furosemide
Antiepileptic Drugs
Tiagabine
Concomitant drug has no effect on the pharmacokinetics of pregabalin
and pregabalin has no effect on the pharmacokinetics of concomitant
drug
Antiepileptic Drugs
Carbamazepine, lamotrigine, phenobarbital,
phenytoin, topiramate, valproic acid
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
Carcinogenesis
A dose-dependent increase in the incidence of malignant vascular tumors (hemangiosarcomas)
was observed in two strains of mice (B6C3F1 and CD-1) given pregabalin (200, 1000, or 5000
mg/kg) in the diet for two years. Plasma pregabalin exposure (AUC) in mice receiving the lowest
dose that increased hemangiosarcomas was approximately equal to the human exposure at the
maximum recommended dose (MRD) of 600 mg/day. A no-effect dose for induction of
hemangiosarcomas in mice was not established. No evidence of carcinogenicity was seen in two
studies in Wistar rats following dietary administration of pregabalin for two years at doses (50,
150, or 450 mg/kg in males and 100, 300, or 900 mg/kg in females) that were associated with
plasma exposures in males and females up to approximately 14 and 24 times, respectively,
human exposure at the MRD.
Mutagenesis
Pregabalin was not mutagenic in bacteria or in mammalian cells in vitro, was not clastogenic in
mammalian systems in vitro and in vivo, and did not induce unscheduled DNA synthesis in
mouse or rat hepatocytes.
Impairment of Fertility
In fertility studies in which male rats were orally administered pregabalin (50 to 2500 mg/kg)
prior to and during mating with untreated females, a number of adverse reproductive and
developmental effects were observed. These included decreased sperm counts and sperm
motility, increased sperm abnormalities, reduced fertility, increased preimplantation embryo loss,
decreased litter size, decreased fetal body weights, and an increased incidence of fetal
abnormalities. Effects on sperm and fertility parameters were reversible in studies of this
duration (3–4 months). The no-effect dose for male reproductive toxicity in these studies (100
mg/kg) was associated with a plasma pregabalin exposure (AUC) approximately 3 times human
exposure at the maximum recommended dose (MRD) of 600 mg/day.
In addition, adverse reactions on reproductive organ (testes, epididymides) histopathology were
observed in male rats exposed to pregabalin (500 to 1250 mg/kg) in general toxicology studies of
four weeks or greater duration. The no-effect dose for male reproductive organ histopathology in
rats (250 mg/kg) was associated with a plasma exposure approximately 8 times human exposure
at the MRD.
In a fertility study in which female rats were given pregabalin (500, 1250, or 2500 mg/kg) orally
prior to and during mating and early gestation, disrupted estrous cyclicity and an increased
number of days to mating were seen at all doses, and embryolethality occurred at the highest
dose. The low dose in this study produced a plasma exposure approximately 9 times that in
humans receiving the MRD. A no-effect dose for female reproductive toxicity in rats was not
established.
Human Data
In a double-blind, placebo-controlled clinical trial to assess the effect of pregabalin on sperm
motility, 30 healthy male subjects were exposed to pregabalin at a dose of 600 mg/day. After 3
months of treatment (one complete sperm cycle), the difference between placebo- and
pregabalin-treated subjects in mean percent sperm with normal motility was <4% and neither
group had a mean change from baseline of more than 2%. Effects on other male reproductive
parameters in humans have not been adequately studied.
13.2 Animal Toxicology and/or Pharmacology
Dermatopathy
Skin lesions ranging from erythema to necrosis were seen in repeated-dose toxicology studies in
both rats and monkeys. The etiology of these skin lesions is unknown. At the maximum
recommended human dose (MRD) of 600 mg/day, there is a 2-fold safety margin for the
dermatological lesions. The more severe dermatopathies involving necrosis were associated with
pregabalin exposures (as expressed by plasma AUCs) of approximately 3 to 8 times those
achieved in humans given the MRD. No increase in incidence of skin lesions was observed in
clinical studies.
Ocular Lesions
Ocular lesions (characterized by retinal atrophy [including loss of photoreceptor cells] and/or
corneal inflammation/mineralization) were observed in two lifetime carcinogenicity studies in
Wistar rats. These findings were observed at plasma pregabalin exposures (AUC) ≥2 times those
achieved in humans given the maximum recommended dose of 600 mg/day. A no-effect dose for
ocular lesions was not established. Similar lesions were not observed in lifetime carcinogenicity
studies in two strains of mice or in monkeys treated for 1 year.
14 CLINICAL STUDIES
14.1 Neuropathic Pain Associated with Diabetic Peripheral Neuropathy
The efficacy of the maximum recommended dose of LYRICA for the management of
neuropathic pain associated with diabetic peripheral neuropathy was established in three doubleblind, placebo-controlled, multicenter studies with three times a day dosing, two of which
studied the maximum recommended dose. Patients were enrolled with either Type 1 or Type 2
diabetes mellitus and a diagnosis of painful distal symmetrical sensorimotor polyneuropathy for
1 to 5 years. A total of 89% of patients completed Studies DPN 1 and DPN 2. The patients had a
minimum mean baseline pain score of ≥4 on an 11-point numerical pain rating scale ranging
from 0 (no pain) to 10 (worst possible pain). The baseline mean pain scores across the two
studies ranged from 6.1 to 6.7. Patients were permitted up to 4 grams of acetaminophen per day
as needed for pain, in addition to pregabalin. Patients recorded their pain daily in a diary.
Study DPN 1: This 5-week study compared LYRICA 25, 100, or 200 mg three times a day with
placebo. Treatment with LYRICA 100 and 200 mg three times a day statistically significantly
improved the endpoint mean pain score and increased the proportion of patients with at least a
50% reduction in pain score from baseline. There was no evidence of a greater effect on pain
scores of the 200 mg three times a day dose than the 100 mg three times a day dose, but there
was evidence of dose dependent adverse reactions [see Adverse Reactions (6.1)]. For a range of
levels of improvement in pain intensity from baseline to study endpoint, Figure 1 shows the
fraction of patients achieving that level of improvement. The figure is cumulative, so that
patients whose change from baseline is, for example, 50%, are also included at every level of
improvement below 50%. Patients who did not complete the study were assigned 0%
improvement. Some patients experienced a decrease in pain as early as Week 1, which persisted
throughout the study.
Figure 1: Patients Achieving Various Levels of Improvement in Pain Intensity – Study DPN 1
Study DPN 2: This 8-week study compared LYRICA 100 mg three times a day with placebo.
Treatment with LYRICA 100 mg three times a day statistically significantly improved the
endpoint mean pain score and increased the proportion of patients with at least a 50% reduction
in pain score from baseline. For various levels of improvement in pain intensity from baseline to
study endpoint, Figure 2 shows the fraction of patients achieving that level of improvement. The
figure is cumulative, so that patients whose change from baseline is, for example, 50%, are also
included at every level of improvement below 50%. Patients who did not complete the study
were assigned 0% improvement. Some patients experienced a decrease in pain as early as Week
1, which persisted throughout the study.
Figure 2: Patients Achieving Various Levels of Improvement in Pain Intensity– Study DPN 2
14.2 Postherpetic Neuralgia
The efficacy of LYRICA for the management of postherpetic neuralgia was established in three
double-blind, placebo-controlled, multicenter studies. These studies enrolled patients with
neuralgia persisting for at least 3 months following healing of herpes zoster rash and a minimum
baseline score of ≥4 on an 11-point numerical pain rating scale ranging from 0 (no pain) to 10
(worst possible pain). Seventy-three percent of patients completed the studies. The baseline mean
pain scores across the 3 studies ranged from 6 to 7. Patients were permitted up to 4 grams of
acetaminophen per day as needed for pain, in addition to pregabalin. Patients recorded their pain
daily in a diary.
Study PHN 1: This 13-week study compared LYRICA 75, 150, and 300 mg twice daily with
placebo. Patients with creatinine clearance (CLcr) between 30 to 60 mL/min were randomized to
75 mg, 150 mg, or placebo twice daily. Patients with creatinine clearance greater than 60
mL/min were randomized to 75 mg, 150 mg, 300 mg or placebo twice daily. In patients with
creatinine clearance greater than 60 mL/min treatment with all doses of LYRICA statistically
significantly improved the endpoint mean pain score and increased the proportion of patients
with at least a 50% reduction in pain score from baseline. Despite differences in dosing based on
renal function, patients with creatinine clearance between 30 to 60 mL/min tolerated LYRICA
less well than patients with creatinine clearance greater than 60 mL/min as evidenced by higher
rates of discontinuation due to adverse reactions. For various levels of improvement in pain
intensity from baseline to study endpoint, Figure 3 shows the fraction of patients achieving that
level of improvement. The figure is cumulative, so that patients whose change from baseline is,
for example, 50%, are also included at every level of improvement below 50%. Patients who did
not complete the study were assigned 0% improvement. Some patients experienced a decrease in
pain as early as Week 1, which persisted throughout the study.
Figure 3: Patients Achieving Various Levels of Improvement in Pain Intensity– Study PHN 1
Study PHN 2: This 8-week study compared LYRICA 100 or 200 mg three times a day with
placebo, with doses assigned based on creatinine clearance. Patients with creatinine clearance
between 30 to 60 mL/min were treated with 100 mg three times a day, and patients with
creatinine clearance greater than 60 mL/min were treated with 200 mg three times daily.
Treatment with LYRICA statistically significantly improved the endpoint mean pain score and
increased the proportion of patients with at least a 50% reduction in pain score from baseline.
For various levels of improvement in pain intensity from baseline to study endpoint, Figure 4
shows the fraction of patients achieving those levels of improvement. The figure is cumulative,
so that patients whose change from baseline is, for example, 50%, are also included at every
level of improvement below 50%. Patients who did not complete the study were assigned 0%
improvement. Some patients experienced a decrease in pain as early as Week 1, which persisted
throughout the study.
Figure 4: Patients Achieving Various Levels of Improvement in Pain Intensity – Study PHN 2
Study PHN 3: This 8-week study compared LYRICA 50 or 100 mg three times a day with
placebo with doses assigned regardless of creatinine clearance. Treatment with LYRICA 50 and
100 mg three times a day statistically significantly improved the endpoint mean pain score and
increased the proportion of patients with at least a 50% reduction in pain score from baseline.
Patients with creatinine clearance between 30 to 60 mL/min tolerated LYRICA less well than
patients with creatinine clearance greater than 60 mL/min as evidenced by markedly higher rates
of discontinuation due to adverse reactions. For various levels of improvement in pain intensity
from baseline to study endpoint, Figure 5 shows the fraction of patients achieving that level of
improvement. The figure is cumulative, so that patients whose change from baseline is, for
example, 50%, are also included at every level of improvement below 50%. Patients who did not
complete the study were assigned 0% improvement. Some patients experienced a decrease in
pain as early as Week 1, which persisted throughout the study.
Figure 5: Patients Achieving Various Levels of Improvement in Pain Intensity– Study PHN 3
14.3 Adjunctive Therapy for Adult Patients with Partial Onset Seizures
The efficacy of LYRICA as adjunctive therapy in partial onset seizures was established in three
12-week, randomized, double-blind, placebo-controlled, multicenter studies in adult patients.
Patients were enrolled who had partial onset seizures with or without secondary generalization
and were not adequately controlled with 1 to 3 concomitant antiepileptic drugs (AEDs). Patients
taking gabapentin were required to discontinue gabapentin treatment 1 week prior to entering
baseline. During an 8-week baseline period, patients had to experience at least 6 partial onset
seizures with no seizure-free period exceeding 4 weeks. The mean duration of epilepsy was 25
years in these 3 studies and the mean and median baseline seizure frequencies were 22.5 and 10
seizures per month, respectively. Approximately half of the patients were taking 2 concurrent
AEDs at baseline. Among the LYRICA-treated patients, 80% completed the double-blind phase
of the studies.
Table 8 shows median baseline seizure rates and median percent reduction in seizure frequency
by dose.
Table 8. Seizure Response in Controlled, Add-On Epilepsy Studies
Daily Dose of
Pregabalin
Study E1
Placebo
50 mg/day
150 mg/day
300 mg/day
600 mg/day
Study E2
Placebo
150 mg/day
600 mg/day
Study E3
Placebo
600 mg/day
600 mg/day
Dosing
Regimen
N
Baseline Seizure
Frequency/mo
Median %
Change from
Baseline
p-value, vs.
placebo
BID
BID
BID
BID
BID
100
88
86
90
89
9.5
10.3
8.8
9.8
9.0
0
-9
-35
-37
-51
0.4230
0.0001
0.0001
0.0001
TID
TID
TID
96
99
92
9.3
11.5
12.3
1
-17
-43
0.0007
0.0001
BID/TID 98
BID
103
TID
111
11
9.5
10
-1
-36
-48
0.0001
0.0001
In the first study (E1), there was evidence of a dose-response relationship for total daily doses of
Lyrica between 150 and 600 mg/day; a dose of 50 mg/day was not effective. In the first study
(E1), each daily dose was divided into two equal doses (twice a day dosing). In the second study
(E2), each daily dose was divided into three equal doses (three times a day dosing). In the third
study (E3), the same total daily dose was divided into two equal doses for one group (twice a day
dosing) and three equal doses for another group (three times a day dosing). While the three times
a day dosing group in Study E3 performed numerically better than the twice a day dosing group,
this difference was small and not statistically significant.
A secondary outcome measure included the responder rate (proportion of patients with ≥50%
reduction from baseline in partial seizure frequency). The following figure displays responder
rate by dose for two of the studies.
Figure 6: Responder rate by add-on epilepsy study
Figure 7: Seizure Reduction by Dose (All Partial Onset Seizures) for Studies E1, E2, and E3
Subset evaluations of the antiseizure efficacy of LYRICA showed no clinically important
differences as a function of age, gender, or race.
14.4 Management of Fibromyalgia
The efficacy of LYRICA for management of fibromyalgia was established in one 14-week,
double-blind, placebo-controlled, multicenter study (F1) and one six-month, randomized
withdrawal study (F2). Studies F1 and F2 enrolled patients with a diagnosis of fibromyalgia
using the American College of Rheumatology (ACR) criteria (history of widespread pain for 3
months, and pain present at 11 or more of the 18 specific tender point sites). The studies showed
a reduction in pain by visual analog scale. In addition, improvement was demonstrated based on
a patient global assessment (PGIC), and on the Fibromyalgia Impact Questionnaire (FIQ).
Study F1: This 14-week study compared LYRICA total daily doses of 300 mg, 450 mg and 600
mg with placebo. Patients were enrolled with a minimum mean baseline pain score of greater
than or equal to 4 on an 11-point numeric pain rating scale and a score of greater than or equal to
40 mm on the 100 mm pain visual analog scale (VAS). The baseline mean pain score in this trial
was 6.7. Responders to placebo in an initial one-week run-in phase were not randomized into
subsequent phases of the study. A total of 64% of patients randomized to LYRICA completed
the study. There was no evidence of a greater effect on pain scores of the 600 mg daily dose than
the 450 mg daily dose, but there was evidence of dose-dependent adverse reactions [see Adverse
Reactions (6.1)]. Some patients experienced a decrease in pain as early as Week 1, which
persisted throughout the study. The results are summarized in Figure 8 and Table 9.
For various levels of improvement in pain intensity from baseline to study endpoint, Figure 8
shows the fraction of patients achieving that level of improvement. The figure is cumulative.
Patients who did not complete the study were assigned 0% improvement. Some patients
experienced a decrease in pain as early as Week 1, which persisted throughout the study.
Figure 8: Patients Achieving Various Levels of Improvement in Pain Intensity – Fibromyalgia
Study F1
Pregabalin 600mg daily dose
Pregabalin 450mg daily dose
Pregabalin 300mg daily dose
Placebo
100
Percent of Patients Improved
90
80
70
60
50
40
30
20
10
0
>0
10
20
30
40
50
60
70
80
90
100
Percent Improvement in Pain from Baseline
Table 9. Patient Global Response in Fibromyalgia Study F1
Patient Global Impression of Change
Treatment
Group
(mg/day)
Placebo
PGB 300
PGB 450
PGB 600
% Any Improvement
47.6
68.1
77.8
66.1
95% CI
(40.0,55.2)
(60.9, 75.3)
(71.5, 84.0)
(59.1, 73.1)
PGB = Pregabalin
Study F2: This randomized withdrawal study compared LYRICA with placebo. Patients were
titrated during a 6-week open-label dose optimization phase to a total daily dose of 300 mg, 450
mg, or 600 mg. Patients were considered to be responders if they had both: 1) at least a 50%
reduction in pain (VAS) and, 2) rated their overall improvement on the PGIC as "much
improved" or "very much improved.” Those who responded to treatment were then randomized
in the double-blind treatment phase to either the dose achieved in the open-label phase or to
placebo. Patients were treated for up to 6 months following randomization. Efficacy was
assessed by time to loss of therapeutic response, defined as 1) less than 30% reduction in pain
(VAS) from open-label baseline during two consecutive visits of the double-blind phase, or 2)
worsening of FM symptoms necessitating an alternative treatment. Fifty-four percent of patients
were able to titrate to an effective and tolerable dose of LYRICA during the 6-week open-label
phase. Of the patients entering the randomized treatment phase assigned to remain on LYRICA,
38% of patients completed 26 weeks of treatment versus 19% of placebo-treated patients.
When considering return of pain or withdrawal due to adverse events as loss of response (LTR),
treatment with LYRICA resulted in a longer time to loss of therapeutic response than treatment
with placebo. Fifty-three percent of the pregabalin-treated subjects compared to 33% of placebo
patients remained on study drug and maintained a therapeutic response to Week 26 of the study.
Treatment with LYRICA also resulted in a longer time to loss of response based on the FIQ1, and
longer time to loss of overall assessment of patient status, as measured by the PGIC2.
1
Time to worsening of the FIQ was defined as the time to a 1-point increase from double-blind baseline in each of the subscales,
and a 5-point increase from double-blind baseline evaluation for the FIQ total score.
2
Time to PGIC lack of improvement was defined as time to PGIC assessments indicating less improvement than “much
improvement.”
Figure 9: Time to Loss of Therapeutic Response, Fibromyalgia Study F2 (Kaplan-Meier
Analysis)
100%
Pregabalin
Placebo
Estimated % Subjects without LTR
90%
80%
70%
60%
50%
40%
30%
20%
10%
0%
0
20
40
60
80
100
120
140
160
180
Days
14.5 Management of Neuropathic Pain Associated with Spinal Cord Injury
The efficacy of LYRICA for the management of neuropathic pain associated with spinal cord
injury was established in two double-blind, placebo-controlled, multicenter studies. Patients were
enrolled with neuropathic pain associated with spinal cord injury that persisted continuously for
at least three months or with relapses and remissions for at least six months. A total of 63% of
patients completed study 1 and 84% completed study 2. The patients had a minimum mean
baseline pain score of ≥4 on an 11-point numerical pain rating scale ranging from 0 (no pain) to
10 (worst possible pain). The baseline mean pain scores across the two studies ranged from 6.5
to 6.7.
Patients were allowed to take opioids, non-opioid analgesics, antiepileptic drugs, muscle
relaxants, and antidepressant drugs if the dose was stable for 30 days prior to screening. Patients
were allowed to take acetaminophen and nonsteroidal anti-inflammatory drugs during the
studies.
Study SCI 1: This 12-week, randomized, double-blind, parallel-group, multicenter, flexible dose
(150-600 mg/day) study compared pregabalin with placebo. The 12-week study consisted of a 3week dose adjustment phase and a 9-week dose maintenance phase. Treatment with LYRICA
150-600 mg/day statistically significantly improved the endpoint weekly mean pain score, and
increased the proportion of patients with at least a 30% and 50% reduction in pain score from
baseline. The fraction of patients achieving various levels of improvement in pain intensity from
baseline to Week 12 is presented in Figure 10. Some patients experienced a decrease in pain as
early as week 1, which persisted throughout the study.
Figure 10: Patients Achieving Various Levels of Improvement in Pain Intensity – Study SCI 1
Study SCI 2: This 16-week, randomized, double-blind, placebo-controlled, parallel-group,
multicenter, flexible dose (150-600 mg/day, in increments of 150 mg) study compared the
efficacy, safety and tolerability of pregabalin with placebo. The 16-week study consisted of a 4week dose adjustment phase and a 12-week dose maintenance phase. Treatment with LYRICA
statistically significantly improved the endpoint weekly mean pain score, and increased the
proportion of patients with at least a 30% and 50% reduction in pain score from baseline. The
fraction of patients achieving various levels of improvement in pain intensity from baseline to
Week 16 is presented in Figure 11. Some patients experienced a decrease in pain as early as
week 1, which persisted throughout the study.
Figure 11: Patients Achieving Various Levels of Improvement in Pain Intensity – Study SCI 2
16 HOW SUPPLIED/STORAGE AND HANDLING
25 mg capsules:
White, hard-gelatin capsule printed with black ink "Pfizer" on the cap, "PGN 25" on the body;
available in:
Bottles of 90:
NDC 0071-1012-68
50 mg capsules:
White, hard-gelatin capsule printed with black ink "Pfizer" on the cap, "PGN 50" and an ink
band on the body, available in:
Bottles of 90:
NDC 0071-1013-68
Unit-Dose Blister Packages of 100:
NDC 0071-1013-41
75 mg capsules:
White/orange hard gelatin capsule printed with black ink "Pfizer" on the cap, "PGN 75" on the
body; available in:
Bottles of 90:
NDC 0071-1014-68
Unit-Dose Blister Packages of 100:
NDC 0071-1014-41
100 mg capsules:
Orange, hard-gelatin capsule printed with black ink "Pfizer" on the cap, "PGN 100" on the body,
available in:
Bottles of 90:
NDC 0071-1015-68
Unit-Dose Blister Packages of 100:
NDC 0071-1015-41
150 mg capsules:
White hard gelatin capsule printed with black ink "Pfizer" on the cap, "PGN 150" on the body,
available in:
Bottles of 90:
NDC 0071-1016-68
Unit-Dose Blister Packages of 100:
NDC 0071-1016-41
200 mg capsules:
Light orange hard gelatin capsule printed with black ink "Pfizer" on the cap, "PGN 200" on the
body, available in:
Bottles of 90:
NDC 0071-1017-68
225 mg capsules:
White/light orange hard gelatin capsule printed with black ink "Pfizer" on the cap, "PGN 225" on
the body; available in:
Bottles of 90:
NDC 0071-1019-68
300 mg capsules:
White/orange hard gelatin capsule printed with black ink "Pfizer" on the cap, "PGN 300" on the
body, available in:
Bottles of 90:
NDC 0071-1018-68
20 mg/mL oral solution:
16 fluid ounce white high density polyethylene (HDPE) bottle with a polyethylene-lined closure:
16 fluid ounce bottle
NDC 0071-1020-01
Storage and Handling
Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) (see USP Controlled
Room Temperature).
See FDA-Approved Medication Guide
17 PATIENT COUNSELING INFORMATION
17.1 Medication Guide
Inform patients of the availability of a Medication Guide, and instruct them to read the
Medication Guide prior to taking LYRICA. Instruct patients to take LYRICA only as prescribed.
17.2 Angioedema
Advise patients that LYRICA may cause angioedema, with swelling of the face, mouth (lip,
gum, tongue) and neck (larynx and pharynx) that can lead to life-threatening respiratory
compromise. Instruct patients to discontinue LYRICA and immediately seek medical care if they
experience these symptoms [see Warnings and Precautions (5.1)].
17.3 Hypersensitivity
Advise patients that LYRICA has been associated with hypersensitivity reactions such as
wheezing, dyspnea, rash, hives, and blisters. Instruct patients to discontinue LYRICA and
immediately seek medical care if they experience these symptoms [see Warnings and
Precautions (5.2)].
17.4 Suicidal Thinking and Behavior
Patients, their caregivers, and families should be counseled that AEDs, including LYRICA, may
increase the risk of suicidal thoughts and behavior and should be advised of the need to be alert
for the emergence or worsening of symptoms of depression, any unusual changes in mood or
behavior, or the emergence of suicidal thoughts, behavior, or thoughts about self-harm. Report
behaviors of concern immediately to healthcare providers [see Warnings and Precautions (5.4)].
17.5 Dizziness and Somnolence
Counsel patients that LYRICA may cause dizziness, somnolence, blurred vision and other CNS
signs and symptoms. Accordingly, advise patients not to drive, operate complex machinery, or
engage in other hazardous activities until they have gained sufficient experience on LYRICA to
gauge whether or not it affects their mental, visual, and/or motor performance adversely. [see
Warnings and Precautions (5.6)].
17.6 Weight Gain and Edema
Counsel patients that LYRICA may cause edema and weight gain. Advise patients that
concomitant treatment with LYRICA and a thiazolidinedione antidiabetic agent may lead to an
additive effect on edema and weight gain. For patients with preexisting cardiac conditions, this
may increase the risk of heart failure. [see Warnings and Precautions (5.5 and 5.7)].
17.7 Abrupt or Rapid Discontinuation
Advise patients to take LYRICA as prescribed. Abrupt or rapid discontinuation may result in
insomnia, nausea, headache, anxiety, hyperhidrosis, or diarrhea. [see Warnings and Precautions
(5.8)].
17.8 Ophthalmological Effects
Counsel patients that LYRICA may cause visual disturbances. Inform patients that if changes in
vision occur, they should notify their physician [see Warnings and Precautions (5.10)].
17.9 Creatine Kinase Elevations
Instruct patients to promptly report unexplained muscle pain, tenderness, or weakness,
particularly if accompanied by malaise or fever. [see Warnings and Precautions (5.11)].
17.10 CNS Depressants
Inform patients who require concomitant treatment with central nervous system depressants such
as opiates or benzodiazepines that they may experience additive CNS side effects, such as
somnolence [see Warnings and Precautions (5.6) and Drug Interactions (7)].
17.11 Alcohol
Tell patients to avoid consuming alcohol while taking LYRICA, as LYRICA may potentiate the
impairment of motor skills and sedating effects of alcohol.
17.12 Use in Pregnancy
Instruct patients to notify their physician if they become pregnant or intend to become pregnant
during therapy, and to notify their physician if they are breast feeding or intend to breast feed
during therapy [see Use In Specific Populations (8.1) and (8.3)].
Encourage patients to enroll in the NAAED Pregnancy Registry if they become pregnant. This
registry is collecting information about the safety of antiepileptic drugs during pregnancy. To
enroll, patients can call the toll free number 1-888-233-2334 [see Use In Specific Populations
(8.1)].
17.13 Male Fertility
Inform men being treated with LYRICA who plan to father a child of the potential risk of malemediated teratogenicity. In preclinical studies in rats, pregabalin was associated with an
increased risk of male-mediated teratogenicity. The clinical significance of this finding is
uncertain [see Nonclinical Toxicology (13.1)].
17.14 Dermatopathy
Instruct diabetic patients to pay particular attention to skin integrity while being treated with
LYRICA. Some animals treated with pregabalin developed skin ulcerations, although no
increased incidence of skin lesions associated with LYRICA was observed in clinical trials [see
Nonclinical Toxicology (13.2)].
LAB-0294-23.0
MEDICATION GUIDE
LYRICA (LEER-i-kah)
(pregabalin)
Capsules and Oral Solution, CV
Read this Medication Guide before you start taking LYRICA and each time you get a refill.
There may be new information. This information does not take the place of talking to your
healthcare provider about your medical condition or treatment. If you have any questions about
LYRICA, ask your healthcare provider or pharmacist.
What is the most important information I should know about LYRICA?
LYRICA may cause serious side effects including:

Serious, even life-threatening, allergic reactions

Suicidal thoughts or actions

Swelling of your hands, legs and feet

Dizziness and sleepiness
These serious side effects are described below:
1. Serious, even life-threatening, allergic reactions.
Stop taking LYRICA and call your healthcare provider right away if you have any of
these signs of a serious allergic reaction:
 swelling of your face, mouth, lips, gums, tongue, throat or neck
 trouble breathing
 rash, hives (raised bumps) or blisters
2. Like other antiepileptic drugs, LYRICA may cause suicidal thoughts or actions in a
very small number of people, about 1 in 500.
Call a healthcare provider right away if you have any of these symptoms, especially if
they are new, worse, or worry you:
 thoughts about suicide or dying
 attempts to commit suicide
 new or worse depression
 new or worse anxiety
 feeling agitated or restless
 panic attacks
 trouble sleeping (insomnia)
 new or worse irritability
 acting aggressive, being angry, or violent



acting on dangerous impulses
an extreme increase in activity and talking (mania)
other unusual changes in behavior or mood
If you have suicidal thoughts or actions, do not stop LYRICA without first talking
to a healthcare provider.

Stopping LYRICA suddenly can cause serious problems.

Suicidal thoughts or actions can be caused by things other than medicines. If
you have suicidal thoughts or actions, your healthcare provider may check for
other causes.
How can I watch for early symptoms of suicidal thoughts and actions?

Pay attention to any changes, especially sudden changes, in mood, behaviors,
thoughts, or feelings.

Keep all follow-up visits with your healthcare provider as scheduled.

Call your healthcare provider between visits as needed, especially if you are
worried about symptoms.
3. Swelling of your hands, legs and feet. This swelling can be a serious problem for people
with heart problems.
4. Dizziness and sleepiness.
Do not drive a car, work with machines, or do other dangerous activities until you know
how LYRICA affects you. Ask your healthcare provider about when it will be okay to do
these activities.
What is LYRICA?
LYRICA is a prescription medicine used in adults, 18 years and older, to treat:

pain from damaged nerves (neuropathic pain) that happens with diabetes

pain from damaged nerves (neuropathic pain) that follows healing of shingles

partial seizures when taken together with other seizure medicines

fibromyalgia (pain all over your body)

pain from damaged nerves (neuropathic pain) that follows spinal cord injury
LYRICA has not been studied in children under 18 years of age.
Who Should Not Take LYRICA?
Do not take LYRICA if you are allergic to pregabalin or any of the ingredients in
LYRICA.
See “What is the most important information I should know about LYRICA?” for the signs of an
allergic reaction.
See the end of this leaflet for a complete list of ingredients in LYRICA.
What should I tell my healthcare provider before taking LYRICA?
Before taking LYRICA, tell your healthcare provider about all your medical conditions,
including if you:

have or have had depression, mood problems or suicidal thoughts or behavior

have kidney problems or get kidney dialysis

have heart problems including heart failure

have a bleeding problem or a low blood platelet count

have abused prescription medicines, street drugs, or alcohol in the past

have ever had swelling of your face, mouth, tongue, lips, gums, neck, or throat
(angioedema)

plan to father a child. Animal studies have shown that pregabalin, the active ingredient in
LYRICA, made male animals less fertile and caused sperm to change. Also, in animal
studies, birth defects were seen in the offspring (babies) of male animals treated with
pregabalin. It is not known if these problems can happen in people who take LYRICA.

are pregnant or plan to become pregnant. It is not known if LYRICA will harm
your unborn baby. You and your healthcare provider will have to decide if you should
take LYRICA while you are pregnant. If you become pregnant while taking LYRICA,
talk to your healthcare provider about registering with the North American Antiepileptic
Drug Pregnancy Registry. You can enroll in this registry by calling 1-888-233-2334. The
purpose of this registry is to collect information about the safety of antiepileptic drugs
during pregnancy.

are breastfeeding. It is not known if LYRICA passes into breast milk and if it can
harm your baby. You and your healthcare provider should discuss whether you should
take LYRICA or breast-feed, but you should not do both
Tell your healthcare provider about all the medicines you take including prescription and nonprescription medicines, vitamins or herbal supplements. LYRICA and other medicines may
affect each other causing side effects. Especially tell your healthcare provider if you take:

angiotensin converting enzyme (ACE) inhibitors, which are used to treat many
conditions, including high blood pressure. You may have a higher chance for swelling
and hives if these medicines are taken with LYRICA. See "What is the most important
information I should know about LYRICA?"

Avandia (rosiglitazone), Avandamet (contains rosiglitazone and metformin), or Actos
(pioglitazone) for diabetes. You may have a higher chance of weight gain or swelling of
your hands or feet if these medicines are taken with LYRICA. See "What are the possible
side effects of LYRICA."

any narcotic pain medicine (such as oxycodone), tranquilizers or medicines for anxiety
(such as lorazepam). You may have a higher chance for dizziness and sleepiness if these
medicines are taken with LYRICA.

any medicines that make you sleepy
Know the medicines you take. Keep a list of them with you to show your healthcare provider and
pharmacist each time you get a new medicine. Do not start a new medicine without talking with
your healthcare provider.
How should I take LYRICA?


Take LYRICA exactly as prescribed. Your healthcare provider will tell you how much
LYRICA to take and when to take it. Take LYRICA at the same times each day.
LYRICA may be taken with or without food.

Your healthcare provider may change your dose. Do not change your dose without
talking to your healthcare provider.

Do not stop taking LYRICA without talking to your healthcare provider. If you stop
taking LYRICA suddenly you may have headaches, nausea, diarrhea, trouble sleeping,
increased sweating, or you may feel anxious. If you have epilepsy and you stop taking
LYRICA suddenly, you may have seizures more often. Talk with your healthcare
provider about how to stop LYRICA slowly.

If you miss a dose, take it as soon as you remember. If it is almost time for your next
dose, just skip the missed dose. Take the next dose at your regular time. Do not take two
doses at the same time.

If you take too much LYRICA, call your healthcare provider or poison control center, or
go to the nearest emergency room right away.
What should I avoid while taking LYRICA?

Do not drive a car, work with machines, or do other dangerous activities until you
know how LYRICA affects you.

Do not drink alcohol while taking LYRICA. LYRICA and alcohol can affect each
other and increase side effects such as sleepiness and dizziness.
What are the possible side effects of LYRICA?
LYRICA may cause serious side effects, including:

See “What is the most important information I should know about LYRICA?"

muscle problems, muscle pain, soreness, or weakness. If you have these symptoms,
especially if you feel sick and have a fever, tell your healthcare provider right away.

problems with your eyesight, including blurry vision. Call your healthcare provider if
you have any changes in your eyesight.

weight gain. If you have diabetes, weight gain may affect the management of your
diabetes. Weight gain can also be a serious problem for people with heart problems.

feeling “high”
The most common side effects of LYRICA are:
 dizziness
 blurry vision
 weight gain
 sleepiness
 trouble concentrating
 swelling of hands and feet
 dry mouth
LYRICA caused skin sores in animal studies. Skin sores did not happen in studies in people. If
you have diabetes, you should pay attention to your skin while taking LYRICA and tell your
healthcare provider about any sores or skin problems.
Tell your healthcare provider about any side effect that bothers you or that does not go away.
These are not all the possible side effects of LYRICA. For more information, ask your healthcare
provider or pharmacist.
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1800-FDA-1088.
How should I store LYRICA?

Store LYRICA capsules and oral solution at room temperature, 59oF to 86°F (15oC to
30°C) in its original package.

Safely throw away any LYRICA that is out of date or no longer needed.

Keep LYRICA and all medicines out of the reach of children.
General information about LYRICA
Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide.
Do not use LYRICA for a condition for which it was not prescribed. Do not give LYRICA to
other people, even if they have the same symptoms you have. It may harm them.
This Medication Guide summarizes the most important information about LYRICA. If you
would like more information, talk with your healthcare provider. You can ask your healthcare
provider or pharmacist for information about LYRICA that is written for health professionals.
You can also visit the LYRICA website at www.LYRICA.com or call 1-866-459-7422 (1-8664LYRICA).
What are the ingredients In LYRICA?
Active ingredient: pregabalin
Inactive ingredients:
LYRICA capsules: lactose monohydrate, cornstarch, talc
Capsule shell: gelatin and titanium dioxide; Orange capsule shell: red iron oxide; White capsule
shell: sodium lauryl sulfate, colloidal silicon dioxide. Colloidal silicon dioxide is a
manufacturing aid that may or may not be present in the capsule shells.
Imprinting ink: shellac, black iron oxide, propylene glycol, potassium hydroxide.
LYRICA oral solution: methylparaben, propylparaben, monobasic sodium phosphate
anhydrous, dibasic sodium phosphate anhydrous, sucralose, artificial strawberry #11545 and
purified water.
This Medication Guide has been approved by the U.S. Food and Drug Administration.
LAB-0299-12.0
Revised: 12/2013